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High Grade CANNABIS BIBLIOGRAPHY SORTED AND ALPHABETIZED BY SUBJECT

Rico Swazi

Active member
Great asset to have available and much appreciated Sam.

Having trouble searching for documents on intra-plant genetic diversity and genetic mosaicism
like this one

https://www.biorxiv.org/content/10.1...823v3.full.pdf. THIS PAPER IS IN THE BIB -SamS
those keywords in the search window put me to the top of the right section, but having to scroll down gets old.
Not found that paper as yet

what am I doing wrong? I would like to go to the corresponding literature for the keywords entered if possible


Here is another I found that you may already have DID NOT HAVE IT BUT ADDED NOW. -SamS

https://mdpi-res.com/d_attachment/pl...0-01794-v2.pdf
 
Last edited by a moderator:

goingrey

Well-known member
Great asset to have available and much appreciated Sam.

Having trouble searching for documents on intra-plant genetic diversity and genetic mosaicism
like this one

https://www.biorxiv.org/content/10.1101/2021.02.11.430823v3.full.pdf
those keywords in the search window put me to the top of the right section, but having to scroll down gets old.
Not found that paper as yet

what am I doing wrong? I would like to go to the corresponding literature for the keywords entered if possible


Here is another I found that you may already have

https://mdpi-res.com/d_attachment/plants/plants-10-01794/article_deploy/plants-10-01794-v2.pdf

You mean here on ICMag? Once you're in the right section use your browser's built in search (keyboard shortcut Ctrl-F on most browsers or something along the lines of "Find" in the menu).
 

Lost Guy

Member
Having trouble logging into IC as Sam_Skunkman so I did this, I will add them to the BIB as soon as I can access my account again. Maybe I need help to access my account? Please help me. -SamS

28 New articles added to IC BIB

2 in IC Breeding Cannabis
3 in IC Legal
6 in IC Medical Cannabis/Endocannabinoids Pt 1 A-D
16 in IC Medical Cannabis/Endocannabinoids Pt 2 E-Z
1 in IC Terpenes



IC Breeding Cannabis

Not Cannabis Specific
Artificially induced polyploidization in Humulus lupulus L. and its effect on morphological and chemical traits

Anna Trojak-Goluch and Urszula Skomra
Breeding Science 63: 393–399 (2013)
doi:10.1270/jsbbs.63.393
https://www.jstage.jst.go.jp/article.../_pdf/-char/en
Chemically induced polyploids were obtained by the colchicine treatment of shoot tips of Humulus lupulus L. ‘Sybilla’. Flow cytometry revealed that most of the treatments resulted in the production of tetraploids. The highest number of tetraploids was obtained when explants were immersed in 0.05% colchicine for 48 h. A field experiment was conducted to compare diploid and tetraploid plants and assess the effect of genome polyploidization on the morphological and chemical characteristics. Tetraploids showed significant differences in relation to diploids. They had thinner and shorter shoots. The influence of chromosome doubling was also reflected in the length, width and area of leaves. The length of female flowers in the tetraploids was significantly shorter than that observed in diploids. Tetraploids produced a diverse number of lupuline glands that were almost twice as large as those observed in diploids. The most distinct effect of genome polyploidization was a significant increase in the weight of cones and spindles. Contents of major chemical constituents of hop cones was little affected by ploidy level. Total essential oils were significantly lower than those in diploids. However there was a significant increase in the proportion of humulene, caryophyllene and farnesene, oils desired by the brewing industry.

Not Cannabis Specific
BREEDING AND GENETICS Development of an Improved Method of Mitotic Metaphase Chromosome Preparation Compatible for Fluorescence in situ Hybridization in Cotton

Ryan J. Andres and Vasu Kuraparthy
The Journal of Cotton Science 17:149–156 (2013)
https://www.researchgate.net/publica...tion_in_Cotton
Molecular cytogenetic techniques, especially Fluorescence In situ Hybridization (FISH) and Genomic In situ Hybridization (GISH), are excellent tools to study the structure and function of chromosomes, polyploidy, aneuploidy, alien gene introgression and genome evolution and physical mapping of genes. For many applications, in situ hybridizations require reliable and efficient methods of chromosome preparation with well preserved and dispersed chromo-somes and little or no cell wall debris. However, such protocols have not yet been published for cotton mitotic chromosome preparations. In the current study, an improved method for preparing mitotic metaphase chromosomes of tetraploid cotton was developed. Root tips were collected from lab-grown three-day-old cotton seedlings and pre-treated with high-pressure nitrous oxide (N 2 O). Following fixation with acetic acid, root tip meristems were removed, enzymatically digested, gently macerated, and then processed to create suspensions of protoplasts in acetic acid and methanol. Suspended protoplasts were then dropped onto a glass slide in order to distribute the protoplasts and spread the chromosomes. Using this approach, acceptable mitotic indexes and high-quality chromosomal spreads with no cell wall debris were obtained. This drop method of preparing chromosome spreads was tested for its compatibility for in situ hybridization using rDNA as probe in FISH. Additionally, varying pre-treatment times with N 2 O were investigated. Our results show that the combination of a 95-minute N 2 O pre-treatment, a 55-minute enzymatic degradation, and the "drop method" efficiently produce cotton mitotic metaphase

IC Legal

Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders
Orrin Devinsky, Maria Roberta Cilio, Helen Cross, Javier Fernandez-Ruiz, Jacqueline French, Charlotte Hill, Russell Katz, Vincenzo Di Marzo, Didier Jutras-Aswad, William George Notcutt, Jose Martinez-Orgado, Philip J. Robson, Brian G. Rohrback, Elizabeth Thiele, Benjamin Whalley, and Daniel Friedman
Epilepsia. 2014 June ; 55(6): 791–802.
doi:10.1111/epi.12631

https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC4707 667&blobtype=pdf
Objective—To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regards to their relevance to epilepsy and other selected neuropsychiatric disorders. Methods—We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology and data from studies with animal models and human subjects. Results—Cannabis has been used to treat disease since ancient times. Δ9 -THC is the major psychoactive ingredient and cannabidiol (CBD) is the major non-psychoactive ingredient in cannabis. Cannabis and Δ9 -THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. Psychotropic effects of Δ9 -THC limit tolerability. CBD is anticonvulsant in many acute animal models but there is limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of melastatin type 8 channel; the 5-HT1a receptor; the α3 and α1 glycine receptors; and the transient receptor potential of ankyrin type 1 channel. CBD has neuroprotective and antiinflammatory effects. CBD appears to be well tolerated in humans but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:Δ9 -THC medical marijuana have claimed efficacy, but studies were not controlled. Significance—CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted. .

High compliance, a lex lata legalization for the non-medical cannabis industry: How to regulate recreational cannabis in accordance with the Single Convention on narcotic drugs, 1961 March 2022

Kenzi Riboulet-Zemouli
https://www.researchgate.net/publication/359163413_High_compliance_a_le x_lata_legalization_for_the_no nmedical_cannabis_industry_How _to_regulate_recreational_cann abis_in_accordance_with_the_Si ngle_Convention_on_narcotic_dr ugs_1961
In the current legal landscape, it is possible to craft policy that combats drug abuse and drug harms, protects human rights, and complies with international drug control law in good faith, by regulating the recreational uses of cannabis products rather than outlawing them. This essay proposes exactly that solution. The international drug control Conventions establish the international legal regime for cannabis, but they are silent on “recreational” or “adult use.” However, they do include broad exemptions in the case of “other than medical and scientific uses in the context of industry.” They are not prohibition treaties, but Framework Conventions on the Control of Some Medicines within the Medical and Pharmaceutical Sectors. Shortcomings in the history of the drug control Conventions, and the current hegemony of one particular interpretation (articulated around prohibition), may have impacted our interpretive frames and discouraged legal scholarship from the study of these exemptions for non-medical uses, purposefully added in the treaty. Via an applicatory contestation of the Conventions reliant on classical methods of treaty interpretation, this essay underlines the relevance of these exemptions in the context of domestic “cannabis legalization” efforts. The legal scheme which applies to the Cannabis plant and its derivatives is two-fold: (1) activities related to medical and scientific purposes are under control, (2) activities for “other than medical and scientific purposes” are exempt from control, provided that two requirements are met: implement effective measures to avoid harms & provide reasonable statistical reporting to the INCB. This existing, good faith, legitimate international legal regime for adult-use cannabis opens an alternative pathway for decision-makers, appeasing rule tension and rerouting international relations on Cannabis matters onto less conflictual tracks

South Dakota: Governor Signs Legislation Preserving Limited Home Grow Rights for Patients
BY NORML MARCH 24, 2022
HTTPS://NORML.ORG/NEWS/2022/03/24/SOUTH-DAKOTA-GOVERNOR-SIGNS-LEGISLATION-PRESERVING-LIMITED-HOME-GROW-RIGHTS-FOR-PATIENTS/

Pierre, SD: Republican Gov. Kristi Noem has signed legislation (SB 24) into law preserving the ability of qualified patients to home cultivate limited quantities of cannabis.
Voters in November 2020 overwhelmingly decided in favor of a ballot initiative (Measure 26) permitting qualified patients to possess, grow, and purchase medical cannabis — a measure which Gov. Noem opposed. Since that time, on two occasions, House lawmakers have voted in favor of legislation to eliminate patients’ home cultivation rights.
“Permitting limited home cultivation provides patients with the ability to have reliable, affordable, and consistent access to their medicine,” NORML’s Deputy Director Paul Armentano said. “Seventy percent of voters approved this right at the ballot box and it is reassuring to see that a majority of lawmakers, and the Governor, ultimately decided to respect the voters’ decision.”
Senate Bill 24, as amended in conference committee, permits registered patients to cultivate a total of four marijuana plants (two mature, two immature) and to legally possess the harvest from those plants.

IC Medical Cannabis/Endocannabinoids Pt 1 A-D

2-Arachidonoylglycerol Attenuates Myocardial Fibrosis in Diabetic Mice Via the TGF-β1/Smad Pathway
Zhengjie Chen & Liangyu Zheng & Gang Chen
Cardiovascular Drugs and TherapyAccepted: 21 December 2021
https://link.springer.com/content/pd...21-07307-7.pdf
Purpose Diabetic cardiomyopathy (DM) is the cause of late cardiac dysfunction in diabetic patients. Myocardial fibrosis is the main pathological mechanism, and it is associated with transforming growth factor-β1(TGF-β1) expression up-regulation. 2- Arachidonoylglycerol (2-AG) is an endogenous cannabinoid that can effectively improve myocardial cell energy metabolism and cardiac function. Here, we evaluated the protective effect of 2-AG on diabetic cardiomyopathy. Methods Male C57BL/6 mice were injected with 2-AG intraperitoneally for 4 weeks (10 micro g/kg/day) after 12 weeks of diabetic modeling. After 4 weeks, heart function was evaluated by echocardiography. Heart structure was assessed by hematoxylin and eosin staining. Cardiac fibrosis was analyzed using immunohistochemistry, Sirius red stain, and western blot. Results After modeling in diabetic mice, cardiac ultrasonography showed decreased cardiac function and pathological findings showed myocardial fibrosis. 2-AG could effectively inhibit the up-regulation of TGF-β1 and Smad2/3, reduce myocardial fibrosis, and ultimately improve cardiac function in diabetic mice. Conclusion 2-AG reduces cardiac fibrosis via the TGF-β1/Smad2/3 pathway and is a potential pathway for the treatment of cardiac dysfunction in diabetic mice. .

Beta-caryophyllene attenuates short-term recurrent seizure activity and blood-brain-barrier breakdown after pilocarpine-induced status epilepticus in rats

Michele Pereira Mallmann, Fernanda Kulinski Mello, Bruna Neuberger, Karine Gabriela da Costa Sobral, Michele Rechia Fighera, Luiz Fernando Freire Royes, Ana Flávia Furian, Mauro Schneider Oliveira
Brain Res. 2022 Mar 14;1784:147883.
doi: 10.1016/j.brainres.2022.147883
Background: Status epilepticus (SE) is a neurological life-threatening condition, resulting from the failure of the mechanisms responsible for seizure termination. SE is often pharmacoresistant and associated with significant morbidity and mortality. Hence, ceasing or attenuating SE and its consequences is of fundamental importance. Beta-caryophyllene is a functional CB2 receptor agonist and exhibit a good safety profile. Besides, it displays beneficial effects in several experimental conditions, including neuroprotective activity. In the present study we aimed to investigate the effects of beta-caryophyllene on pilocarpine-induced SE.
Methods: Wistar rats were submitted to pilocarpine-induced SE and monitored for 24 h by video and EEG for short-term recurrence of seizure activity (i.e. seizures occurring within 24 h after termination of SE). Rats received beta-caryophyllene (100 mg/kg, ip) at 1, 8- and 16-hours after SE. Twenty-four hours after SE we evaluated sensorimotor response, neuronal damage (fluoro jade C staining) and serum albumin infiltration into brain parenchyma.
Results: Beta-caryophyllene-treated animals presented fewer short-term recurrent seizures than vehicle-treated counterparts, suggesting an anticonvulsant effect after SE. Behavioral recovery from SE and the number of fluoro jade C positive cells in the hippocampus and thalamus were not modified by beta-caryophyllene. Treatment with beta-caryophyllene attenuated the SE-induced increase of albumin immunoreactivity in the hippocampus, indicating a protective effect against blood-brain-barrier breakdown.
Conclusions: Given the inherent difficulties in the treatment of SE and its consequences, present results suggest that beta-caryophyllene deserve further investigation as an adjuvant therapeutic strategy for SE.
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Cannabinoids: A new hope for breast cancer therapy?
María M. Caffarel a , Clara Andradas, Eduardo Pérez-Gómez, Manuel Guzmán, Cristina Sánchez
Cancer Treatment Reviews 38 (2012) 911–918
DOI: 10.1016/j.ctrv.2012.06.005
Breast cancer is a very common disease that affects approximately 1 in 10 women at some point in their lives. Importantly, breast cancer cannot be considered a single disease as it is characterized by distinct pathological and molecular subtypes that are treated with different therapies and have diverse clinical outcomes. Although some highly successful treatments have been developed, certain breast tumors are resistant to conventional therapies and a considerable number of them relapse. Therefore, new strategies are urgently needed, and the challenge for the future will most likely be the development of individualized therapies that specifically target each patient’s tumor. Experimental evidence accumulated during the last decade supports that cannabinoids, the active components of Cannabis sativa and their derivatives, possess anticancer activity. Thus, these compounds exert anti-proliferative, pro-apoptotic, antimigratory and anti-invasive actions in a wide spectrum of cancer cells in culture. Moreover, tumor growth, angiogenesis and metastasis are hampered by cannabinoids in xenograft-based and genetically-engineered mouse models of cancer. This review summarizes our current knowledge on the antitumor potential of cannabinoids in breast cancer, which suggests that cannabinoid-based medicines may be useful for the treatment of most breast tumor subtypes .

Cannabinoids and Neuroprotection in Basal Ganglia Disorders
Onintza Sagredo & Moisés García-Arencibia & Eva de Lago & Simone Finetti & Alessandra Decio & Javier Fernández-Ruiz
Mol Neurobiol (2007) 36:82–91
DOI 10.1007/s12035-007-0004-3

Cannabinoids have been proposed as clinically promising neuroprotective molecules, as they are capable to reduce excitotoxicity, calcium influx, and oxidative injury. They are also able to decrease inflammation by acting on glial processes that regulate neuronal survival and to restore blood supply to injured area by reducing the vasoconstriction produced by several endothelium-derived factors. Through one or more of these processes, cannabinoids may provide neuroprotection in different neurodegenerative disorders including Parkinson’s disease and Huntington’s chorea, two chronic diseases that are originated as a consequence of the degeneration of specific nuclei of basal ganglia, resulting in a deterioration of the control of movement. Both diseases have been still scarcely explored at the clinical level for a possible application of cannabinoids to delay the progressive degeneration of the basal ganglia. However, the preclinical evidence seems to be solid and promising. There are two key mechanisms involved in the neuroprotection by cannabinoids in experimental models of these two disorders: first, a cannabinoid receptor-independent mechanism aimed at producing a decrease in the oxidative injury and second, an induction/upregulation of cannabinoid CB2 receptors, mainly in reactive microglia, that is capable to regulate the influence of these glial cells on neuronal homeostasis. Considering the relevance of these preclinical data and the lack of efficient neuroprotective strategies in both disorders, we urge the development of further studies that allow that the promising expectatives generated for these molecules progress from the present preclinical evidence till a real clinical application.

Cannabinoids Block Cellular Entry of SARS-CoV2 and the Emerging Variants
Richard B. van Breemen, Ruth N. Muchiri, Timothy A. Bates, Jules B. Weinstein, Hans C. Leier, Scotland Farley, and Fikadu G. Tafesse
J. Nat. Prod. 2022, 85, 176−184
https://pubs.acs.org/doi/pdf/10.1021...atprod.1c00946

As a complement to vaccines, small-molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, which cause COVID-19. Affinity selection−mass spectrometry was used for the discovery of botanical ligands to the SARS-CoV-2 spike protein. Cannabinoid acids from hemp (Cannabis sativa) were found to be allosteric as well as orthosteric ligands with micromolar affinity for the spike protein. In follow-up virus neutralization assays, cannabigerolic acid and cannabidiolic acid prevented infection of human epithelial cells by a pseudovirus expressing the SARS-CoV-2 spike protein and prevented entry of live SARS-CoV-2 into cells. Importantly, cannabigerolic acid and cannabidiolic acid were equally effective against the SARS-CoV-2 alpha variant B.1.1.7 and the beta variant B.1.351. Orally bioavailable and with a long history of safe human use, these cannabinoids, isolated or in hemp extracts, have the potential to prevent as well as treat infection by SARS-CoV-2. .


Cannabis Use among Patients with Alopecia Areata: A Cross-Sectional Survey Study
Jane J Han, Adam Faletsky, Arash Mostaghimi, Kathie P Huang
Int J Trichology. Jan-Feb 2022;14(1):21-24.
DOI: 10.4103/ijt.ijt_96_21
https://www.ncbi.nlm.nih.gov/pmc/art...er#!po=83.3333
Importance: Little is known about cannabis use among patients with alopecia areata (AA). These patients often experience significant psychosocial burden and may seek alternative therapies beyond that of traditional medical treatments, such as cannabis.
Objective: To characterize cannabis use among patients with AA.
Design: This was a cross-sectional study conducted from March 9, 2021, to March 22, 2021, using a web-based survey distributed to adult patients with AA using the National AA Foundation's email listserv and social media platforms.
Results: 1,087 participants completed the survey (completion rate: 88.1%). Most participants were female (n = 870, 83.3%) and Caucasian (n = 771, 73.8%), with a mean age of 47.6 ± 15.5 years. 65.9% (n = 689) of participants with AA had a history of cannabis use and among those, 51.8% (n = 357) were current cannabis users. The most common reason for cannabis use among current users was for AA-related symptoms (n = 199, 55.7%), with the greatest perceived improvement in symptoms of stress (n = 261, 73.1%) and anxiety, sadness, and depression (n = 234, 65.6%). 80.4% (n = 287) indicated that cannabis had no impact on their hair loss.
Conclusion: Cannabis use is common among patients with AA and is often used to alleviate the psychosocial symptoms related to AA, despite the lack of perceived improvement in hair regrowth
Find PDF link has paper but not PDF

IC Medical Cannabis/Endocannabinoids Pt 2 E-Z

Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability
Mohammad-Reza Ghovanloo, Mark Estacion, Grant P Higerd, Peng Zhao, Sulayman Dib-Hajj, Stephen G Waxman
Br J Pharmacol . 2022 Mar 16.
DOI: 10.1111/bph.15833https://bpspubs.onlinelibrary.wiley... .1111/bph.15833
Background and purpose: Cannabigerol (CBG), a non-psychotropic phytocannabinoid and a precursor for ∆9-tetrahydrocannabinol and cannabidiol, has been suggested to act as an analgesic. A previous study reported that CBG (10 μM) blocks voltage-gated sodium (Nav) currents in CNS neurons; however, the underlying mechanism is not well-understood. Genetic and functional studies have validated Nav1.7 as an opportune target for analgesic drug development. The effects of CBG on Nav1.7 channels, which may contribute to its analgesic properties, have not been previously investigated.
Experimental approach: To determine the effects of CBG on Nav channels, we used stably transfected HEK cells and primary dorsal root ganglion (DRG) neurons to characterize compound effects using experimental and computational techniques. These included patch-clamp, multielectrode array, and action potential modelling.
Key results: We found that CBG is a ~10-fold state-dependent Nav inhibitor (KI -KR : ~2-20 μM) with an average Hill-slope of ~2. We determined that at lower concentrations, CBG predominantly blocks sodium Gmax and slows recovery from inactivation; however, as the concentration is increased, CBG also induces a hyperpolarizing shift in half-voltage of inactivation. Our modeling and multielectrode array recordings suggest that CBG attenuates DRG excitability.
Conclusions and implications: Inhibition of Nav1.7 in DRG neurons may underlie CBG-induced neuronal hypoexcitability. As most Nav1.7 channels are inactivated at DRG resting membrane potential, they are more likely to be inhibited by lower CBG concentrations, suggesting functional selectivity against Nav1.7 compared to other Navs (via Gmax block).
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Is Early Exposure to Cannabis Associated with Bipolar disorder? Results from a Finnish Birth-Cohort Study

Alexander Denissoff, Antti Mustonen, Anni-Emilia Alakokkare, James G Scott, Musa B Sami, Jouko Miettunen, Solja Niemelä
Addiction. 2022 Mar 21.
doi: 10.1111/add.15881.
Background and aims: There are few longitudinal studies assessing the association of cannabis use and subsequent onset of bipolar disorder. We aimed to measure the association between early cannabis exposure and subsequent bipolar disorder.
Design, setting, and participants: Observational study linking a sample from the Northern Finland Birth Cohort 1986 (n=6,325) to nationwide register data to examine the association of life-time cannabis exposure at age 15/16 years and subsequent bipolar disorder until age 33 (until the end of 2018). 6,325 individuals (48.8% males) were included in the analysis.
Measurements: Cannabis exposure was measured via self-report. Bipolar disorder was measured via bipolar disorder-related diagnostic codes (ICD-10: F30.xx, F31.xx) collected from the Care Register for Health Care 2001-2018, the Register of Primary Health Care Visits 2011 - 2018, the medication reimbursement register of the Social Insurance Institution of Finland 2001 - 2005 and the disability pensions of the Finnish Center for Pensions 2001 - 2016. Potential confounders included demographic characteristics, parental psychiatric disorders, emotional and behavioral problems and other substance use.
Findings: 352 adolescents (5.6 %) reported any cannabis use until the age of 15-16 years. Of the whole sample, 66 (1.0 %) were diagnosed with bipolar disorder. Adolescent cannabis use was associated with bipolar disorder (hazard ratio
=3.46; 95% confidence interval [CI] 1.81-6.61). This association remained statistically significant after adjusting for sex, family structure, and parental psychiatric disorders (HR =3.00; 95% CI 1.47-6.13) and after further adjusting for adolescent emotional and behavioral problems (HR =2.34; 95% CI 1.11-4.94). Further adjustments for frequent alcohol intoxications, daily smoking and lifetime illicit drug use attenuated the associations to statistically non-significant.




Conclusions: In Finland, the positive association between early cannabis exposure and subsequent development of bipolar disorder appears to be confounded by other substance use.
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Medical Cannabis for Gilles de la Tourette Syndrome: An Open- Label Prospective Study
Saar Anis , Corinne Zalomek, Amos D. Korczyn, Alina Rosenberg, Nir Giladi, and Tanya Gurevich
Behavioural Neurology Volume 2022, 10 pages
DOI: 10.1155/2022/5141773
https://downloads.hindawi.com/journa...22/5141773.pdf
Objectives. Assessing the effectiveness and tolerability of medical cannabis (MC) treatment on Gilles de la Tourette syndrome (GTS) patients. Methods. We report on an open-label, prospective study on the effect of MC on adult GTS patients. MC mode of use was decided by the treating neurologist and the patient. Δ9-Tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) content within MC product and monthly dose were titrated during the study. Following treatment initiation, patients were assessed after 4 and 12 weeks for efficacy, tolerability, and side effects. Results. Eighteen patients entered the study. Baseline Yale Global Tic Severity Scale- (YGTSS) Total (range 0-100) was 60:3 ± 17:1. Three patients did not reach the end of follow-up period. The most common mode of administration was smoking (80%). Following twelve weeks of treatment, a significant 38% average reduction (p = 0:002) of YGTSS-Total and a 20% reduction (p = 0:043) of Premonitory Urge for Tic Scale (PUTS) were observed. Common side effects were dry mouth (66.7%), fatigue (53.3%), and dizziness (46.7%). Three patients suffered from psychiatric side effects including worsening of obsessive compulsive disorder (stopped treatment), panic attack, and anxiety (resolved with treatment modification). Six patients (40%) reported cognitive side effects regarding time perception, visuospatial disorientation, confusion, slow processing speed, and attention. Conclusions. MC treatment demonstrates good efficacy and tolerability in adult GTS patients. Predilection for smoking rather than using oil drops requires further comparative studies to evaluate the efficacy of each. Cognitive and psychiatric side effects have to be monitored and addressed.

Medical Marijuana Efficacy: A Survey
Ngugi M. Kinyungu, Josiah Gikungi, Ariel Davson
Open Journal of Anesthesiology, 2022, 12, 91-98
https://www.scirp.org/pdf/ojanes_2022030716163914.pdf
Background: Medical marijuana use has seen a rise and acceptance in the last several years and while its efficacy has been spoken and discussed in lore, data on efficacy still remains scarce.
Aim: We conducted a survey on chronic pain patients certified for medical marijuana to assess pain relief and efficacy.
Findings: Our survey found that the pain score with the use of medical marijuana was halved in our 20 respondents and sleep was improved. Overall function improved.
Conclusion: The survey shows that medical marijuana is efficacious in chronic pain patients and further studies need to be done and access to the medication needs to be improved so as to benefit more patients. .

Risk-thresholds for the association between frequency of cannabis use and the development of psychosis: a systematic review and meta-analysis
https://www.cambridge.org/core/journals/psychological-medicine/article/riskthresholds-for-the-association-between-frequency-of-cannabis-use-and-the-development-of-psychosis-a-systematic-review-and-metaanalysis/4EB34100E58C5C9E1370CAFE83C7F7 05
Tessa Robinson, Muhammad Usman Ali, Bethany Easterbrook, Wayne Hall, Didier Jutras-Aswad, and Benedikt Fischer
Published online by Cambridge University Press: 24 March 2022
Background
Epidemiological studies show a dose–response association between cannabis use and the risk of psychosis. This review aimed to determine whether there are identifiable risk-thresholds between the frequency of cannabis use and psychosis development.
Methods
Systematic search of Embase, MEDLINE, PsycINFO, CINAHL, and Web of Science for relevant studies (1 January 2010–26 April 2021). Case–control or cohort studies that investigated the relationship between cannabis use and the risk of psychosis development that reported effect estimates [odds ratios (OR), hazard ratios (HR), risk ratios (RR)] or the raw data to calculate them, with information on the frequency of cannabis consumption were included. Effect estimates were extracted from individual studies and converted to RR. Two-stage dose–response multivariable meta-analytic models were utilized and sensitivity analyses conducted. The Newcastle Ottawa Scale was used to assess the risk of bias of included studies.
Results
Ten original (three cohorts, seven case–control) studies were included, including 7390 participants with an age range of 12–65 years. Random-effect model meta-analyses showed a significant log-linear dose–response association between cannabis use frequency and psychosis development. A restricted cubic-splines model provided the best fit for the data, with the risk of psychosis significantly increasing for weekly or more frequent cannabis use [RR = 1.01, 95% confidence interval (CI) 0.93–1.11 yearly; RR = 1.10, 95% CI 0.97–1.25 monthly; RR = 1.35, 95% CI 1.19–1.52 weekly; RR = 1.76, 95% CI 1.47–2.12 daily]
Conclusion
Individuals using cannabis frequently are at increased risk of psychosis, with no significant risk associated with less frequent use. Public health prevention messages should convey these risk-thresholds, which should be refined through further work.

Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-induced neuropathic pain in rodents
Anil Kumar Kalvala, Arvind Bagde, Peggy Arthur, Sunil Kumar Surapaneni, Nimma Ramesh, Aakash Nathani, Mandip Singh
International Immunopharmacology Volume 107, June 2022
DOI: 10.1016/j.intimp.2022.108693

THCV, when combined with CBD, provides excellent neuroprotection against paclitaxel-induced peripheral neuropathy in mice.

THCV and CBD improve mitochondrial health and neuron function by modulating CB1 and 5HT1A receptors, respectively.

After blocking CB1 and 5HT1A receptors in PTX-injured DRG primary cultures, THCV and CBD have no effect on neurite outgrowths, mitochondrial membrane potentials, or mitochondrial superoxide production.
The purpose of this study was to evaluate if phytocannabinoids, synthetic cannabidiol (CBD), and tetrahydrocannabivarin (THCV), and their combination, could protect mice from Paclitaxel-induced peripheral neuropathy (PIPN). Six groups of C57BL/6J mice (n = 6) were used in this study. The mice were given paclitaxel (PTX) (8 mg/kg/day, i.p.) on days 1, 3, 5, and 7 to induce neuropathy. Mice were evaluated for behavioral parameters, and dorsal root ganglions (DRG) were collected from the animals and subjected to RNA sequencing and westernblot analysis at the end of the study. On cultured DRGs derived from adult male rats, immunocytochemistry and mitochondrial functional assays were also performed. When compared to individual treatments, the combination of CBD and THCV improved thermal and mechanical neurobehavioral symptoms in mice by twofold. Targets for CBD and THCV therapy were identified by KEGG (RNA sequencing). PTX reduced the expression of p-AMPK, SIRT1, NRF2, HO1, SOD2, and catalase while increasing the expression of PI3K, p-AKT, p-P38 MAP kinase, BAX, TGF-β, NLRP3 inflammasome, and caspase 3 in DRG homogenates of mice. Combination therapy outperformed monotherapy in reversing these protein expressions. The addition of CBD and THCV to DRG primary cultures reduced mitochondrial superoxides while increasing mitochondrial membrane potentials. WAY100135 and rimonabant altered the neuroprotective effects of CBD and THCV respectively by blocking 5-HT1A and CB1 receptors in mice and DRG primary cultures. The entourage effect of CBD and THCV against PIPN appears to protect neurons in mice via 5HT1A and CB1 receptors respectively.
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Role of endocannabnoid system in mental diseases
JORGE MANZANARES*, LEYRE URIGÜEN, GABRIEL RUBIO and TOMÁS PALOMO
Neurotoxicity Research, 2004, VOL. 6(3). pp. 001-012
https://www.researchgate.net/publica...endocannabinoi d_system_in_mental_diseases
I
n the last decade, a large number of studies using Δ9-tetrahydrocannabinol (THC), the main active principle derivative of the marijuana plant, or cannabinoid synthetic derivatives have substantially contributed to advance the understanding of the pharmacology and neurobiological mechanisms produced by cannabinoid receptor activation. Cannabis has been historically used to relieve some of the symptoms associated with central nervous system disorders. Nowadays, there are anecdotal evidences for the use of cannabis in many patients suffering from multiple sclerosis or chronic pain. Following the historical reports on the use of cannabis for medicinal purposes, recent research has highlighted the potential of cannabinoids to treat a wide variety of clinical disorders. Some of these disorders that are being investigated are pain, motor dysfunctions, or psychiatric illness. On the other hand, cannabis abuse has been related to several psychiatric disorders such as dependence, anxiety, depression, cognitive impairment, and psychosis. Considering that cannabis or cannabinoid pharmaceutical preparations may no longer be exclusively recreational drugs but may also present potential therapeutic uses, it has become of great interest to analyze the neurobiological and behavioral consequences of their administration. This review attempts to link current understanding of the basic neurobiology of the endocannabi-noid system to novel opportunities for therapeutic intervention and its effects on the central nervous system. .


The anxiolytic effect of cannabidiol depends on the nature of the trauma when patients with post-traumatic stress disorder recall their trigger event
Lívia Maria Bolsoni, José Alexandre S. Crippa,Jaime Eduardo Cecílio HallakFrancisco Silveira Guimarães,Antonio Waldo Zuardi
Braz J Psychiatry (2022)
DOI: 10.1590/1516-4446-2021-2317
https://www.scielo.br/j/rbp/a/y4LLjM...at=pdf&lang=en
Objectives:
We assessed whether administering cannabidiol (CBD) before recalling the traumatic event that triggered their disorder attenuates anxiety in patients with post-traumatic stress disorder (PTSD). As an exploratory pilot analysis, we also investigated whether this effect depends on the nature of the event (sexual vs. nonsexual trauma).
Methods:
Thirty-three patients of both sexes with PTSD were recruited and randomized 1:1 into two groups. One group received oral CBD (300 mg), and the other received a placebo before listening to a digital audio playback of their previously recorded report of the trigger event. Subjective and physiological measurements were taken before and after recall. We analyzed the data in two subsamples: trigger events involving sexual and nonsexual trauma.
Results:
In the nonsexual trauma group, the differences between measurements before and after recall were significantly smaller with CBD than placebo; this held true for anxiety and cognitive impairment. However, in the sexual trauma group, the differences were non-significant for both measurements.
Conclusion:
A single dose of CBD (300mg) attenuated the increased anxiety and cognitive impairment induced by recalling a traumatic event in patients with PTSD when the event involved nonsexual trauma.


The association between cannabis use and depression: a review of the evidence
Louisa Degenhardt, Wayne Hall, Michael Lynskey, Carolyn Coffey and George Patton
chapter 4 in Book Marijuana and madness
Doi: 10.1017/CBO9780511543630.006
The association between cannabis and depression has received less attention than the links between cannabis use and psychosis. Some have suggested that cannabis use may be a contributory cause of suicidal behaviors. A number of studies have found association between cannabis use and suicide, but the quality of control for confounding variables has varied widely. There is increasing evidence that regular cannabis use and depression occur together more often than we might expect by chance. The association between cannabis use and depression may arise because the same factors that predispose people to use cannabis also increase their risk of depression. Cross-sectional and longitudinal studies have provided mixed evidence on the association between cannabis use and depression. There is a need for longitudinal and twin studies that assess the relationship between cannabis use, depression and confounding factors.
,

The cannabinoid receptor-1 gene interacts with stressful life events to increase the risk for problematic alcohol use

Lisa Bornscheuer, Andreas Lundin, Yvonne Forsell, Catharina Lavebratt, Philippe A Melas Nature 2022
https://www.nature.com/articles/s41598-022-08980-w.pdf
Problematic alcohol use is a major contributor to the global burden of death and disabilities, and it represents a public health concern that has grown substantially following the COVID-19 pandemic. The available treatment options remain limited and to develop better pharmacotherapies for alcohol misuse we need to identify suitable biological targets. Previous research has implicated the brain's endocannabinoid system (ECS) in psychiatric and stress-related outcomes, including substance use and habituation to repeated stress. Moreover, genetic variants in the cannabinoid-1 receptor gene (CNR1; CB1R) have been associated with personality traits, which are in turn predictors of substance use disorders. To date, however, no human genome-wide association study has provided evidence for an involvement of the ECS in substance use outcomes. One reason for this ECS-related "missing heritability" may be unexamined gene-environment interactions. To explore this possibility, we conducted cross-sectional analyses using DNA samples and stress-exposure data from a longitudinal Swedish population-based study (N = 2,915). Specifically, we genotyped rs2023239, a functional C/T single nucleotide polymorphism in CNR1, previously reported to be associated with CNR1 binding in the brain, subjective reward following alcohol intake, and alcohol cue-elicited brain activation. Our two outcomes of interest were (i) problematic alcohol use based on the Alcohol Use Disorders Identification Test (AUDIT), and (ii) personality trait scores based on the Five Factor Model. We found no baseline association between rs2023239 and problematic alcohol use or personality traits. However, there was a clear trend for interaction between rs2023239's risk allele (C) and stressful life events (SLEs) in both childhood and adulthood, which predicted problematic alcohol use. Although not significant, there was also some indication that the risk allele interacted with child SLEs to increase scores on neuroticism. Our study supports the notion that the ECS can affect alcohol intake behaviors by interacting with life adversities and is-to the best of our knowledge-the first to focus on the interaction between CNR1 and stressors in both childhood and adulthood in humans. Further studies are warranted to confirm these findings.

The dose-dependent effect of a stabilized cannabidiol nanoemulsion on ocular surface inflammation and intraocular pressure
Leslie Rebibo, Marina Frušić-Zlotkin, Ron Ofri, Taher Nassar,
Int J Pharm. 2022 Apr 5;617:121627
DOI: 10.1016/j.ijpharm.2022.121627
Cannabidiol (CBD) is a phytocannabinoid that has a great clinical therapeutic potential. Few studies have been published on its efficacy in ocular inflammations while its impact on intraocular pressure (IOP), a major risk factor for glaucoma, remains unclear. Moreover, due to its lability and high lipophilicity, its formulation within a prolonged stable topical ophthalmic solution or emulsion able to penetrate the highly selective corneal barrier is challenging. Therefore, various CBD nanoemulsions (NEs) were designed and evaluated for stability in accelerated conditions. Further, the optimal formulation was tested on a murine LPS-induced keratitis inflammation model. Lastly, increasing CBD concentrations were topically applied, for two weeks, on mice eyes, for IOP measurement. CBD NEs exhibited optimal physicochemical characteristics for ocular delivery. A specific antioxidant was required to obtain the stable, final, formulation. In vivo, 0.4 to 1.6% CBD w/v reduced the levels of key inflammatory cytokines, depending on the concentration applied. These concentrations decreased or did not affect the IOP. Our results showed that a well-designed CBD ocular dosage form can be stabilized for an extended shelf life. Furthermore, the significant decrease in inflammatory cytokines levels could be exploited, provided that an adequate therapeutic dosage regimen is identified in humans.
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The Effectiveness of Common Cannabis Products for Treatment of Nausea
Stith, Sarah S. PhD[SUP]*[/SUP]; Li, Xiaoxue PhD[SUP]*[/SUP]; Orozco, Joaquin MS[SUP][/SUP]; Lopez, Victoria BS[SUP][/SUP]; Brockelman, Franco BS[SUP]§[/SUP]; Keeling, Keenan BS[SUP]§[/SUP]; Hall, Branden[SUP]§[/SUP]; Vigil, Jacob M. PhD[SUP][/SUP]
Journal of Clinical Gastroenterology: April 2022 - Volume 56 - Issue 4 - p 331-338
doi: 10.1097/MCG.0000000000001534
Goals:
We measure for the first time how a wide range of cannabis products affect nausea intensity in actual time.
Background:
Even though the Cannabis plant has been used to treat nausea for millennia, few studies have measured real-time effects of common and commercially available cannabis-based products.
Study:
Using the Releaf App, 886 people completed 2220 cannabis self-administration sessions intended to treat nausea between June 6, 2016 and July 8, 2019. They recorded the characteristics of self-administered cannabis products and baseline symptom intensity levels before tracking real-time changes in the intensity of their nausea.
Results:
By 1 hour postconsumption, 96.4% of people had experienced symptom relief with an average symptom intensity reduction of −3.85 points on a 0 to 10 visual analog scale (SD=2.45, d=1.85, P<0.001). Symptom relief was statistically significant at 5 minutes and increased with time. Among product characteristics, flower and concentrates yielded the strongest, yet similar results; products labeled as Cannabis indica underperformed those labeled as Cannabis sativa or hybrid; and joints were associated with greater symptom relief than pipes or vaporizers. In sessions using flower, higher tetrahydrocannbinol and lower cannabidiol were generally associated with greater symptom relief (eg, within 5min).
Conclusions:
The findings suggest that the vast majority of patients self-selecting into cannabis use for treatment of nausea likely experience relief within a relative short duration of time, but the level of antiemetic effect varies with the characteristics of the cannabis products consumed in vivo. Future research should focus on longer term symptom relief, including nausea-free intervals and dosing frequency; the risks of consumption of medical cannabis, especially among high-risk populations, such as pregnant women and children; and potential interactions between cannabis, conventional antiemetics, other medications, food, tobacco, alcohol, and street drugs among specific patient populations.
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The endocannabinoid system and nondrug rewarding behaviours
Liana Fattore, Miriam Melis, Paola Fadda, Marco Pistis, Walter Fratta

Experimental Neurology 224 (2010) 23–36
doi:10.1016/j.expneurol.2010.03.020

https://d1wqtxts1xzle7.cloudfront.net/40529013/The_endocannabinoid_system_and _nondrug_r20151201-3878-1t6az70-libre.pdf?1448957870=&response-content-disposition=inline%3B+filename %3DThe_endocannabinoid_system_ and_nondrug_r.pdf&Expires=1648 399025&Signature=MwC~WQOO1h-eazHdaPsEv6gsvGPKjheCZoRR6XUNt EGHuhTg4YpXCp5fB-K-GETHEi7lF-zg6O21-APPgHZP~gUQxEWgZzn1ABRnX50qi-m2o9EHLMdnILhYduytK~AGtLDEu5Nw 3LqgYZOlFR3aFIx5~4qQ0lnNyL4F9N s9AxLVzqZ02aIb4JLPSORMn-5SkfaC2ENfVeOV6EQywhscsKJyMeMv 6XV97eL4abiLcKdPyePNsNp~~Z0nPN lwLFkvVr0~xUJkXNYZCKRP06971w8g nbb6ZfHBD9nDIBWdwIJEJl32Zsvsbf cxb~nIwvt~LY-Q8jPLj~n~X0swPGroyQ__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA
Rewarding behaviours such as sexual activity, eating, nursing, parenting, social interactions, and play activity are conserved strongly in evolution, and they are essential for development and survival. All of these behaviours are enjoyable and represent pleasant experiences with a high reward value. Remarkably, rewarding behaviours activate the same brain circuits that mediate the positive reinforcing effects of drugs of abuse and of other forms of addiction, such as gambling and food addiction. Given the involvement of the endocannabinoid system in a variety of physiological functions of the nervous system, it is not surprising that it takes part in the complex machinery that regulates gratification and perception of pleasure. In this review, we focus first on the role of the endocannabinoid system in the modulation of neural activity and synaptic functions in brain regions that are involved in natural and nonnatural rewards (namely, the ventral tegmental area, striatum, amygdala, and prefrontal cortex). Then, we examine the role of the endocannabinoid system in modulating behaviours that directly or indirectly activate these brain reward pathways. More specifically, current knowledge of the effects of the pharmacological manipulation of the endocannabinoid system on natural (eating, sexual behaviour, parenting, and social play) and pathological (gambling) rewarding behaviours is summarised and discussed. .
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The endocannabinoid system in brain reward processes
M Solinas, SR Goldberg and D Piomelli

British Journal of Pharmacology (2008) 154, 369–383;
doi:10.1038/bjp.2008.130;

https://escholarship.org/content/qt06v3q9jn/qt06v3q9jn_noSplash_5e1a39c7a2 7c814bfb7a8613533b0bad.pdf
Food, drugs and brain stimulation can serve as strong rewarding stimuli and are all believed to activate common brain circuits that evolved in mammals to favour fitness and survival. For decades, endogenous dopaminergic and opioid systems have been considered the most important systems in mediating brain reward processes. Recent evidence suggests that the endogenous cannabinoid (endocannabinoid) system also has an important role in signalling of rewarding events. First, CB1 receptors are found in brain areas involved in reward processes, such as the dopaminergic mesolimbic system. Second, activation of CB1 receptors by plant-derived, synthetic or endogenous CB1 receptor agonists stimulates dopaminergic neurotransmission, produces rewarding effects and increases rewarding effects of abused drugs and food. Third, pharmacological or genetic blockade of CB1 receptors prevents activation of dopaminergic neurotransmission by several addictive drugs and reduces rewarding effects of food and these drugs. Fourth, brain levels of the endocannabinoids anandamide and 2- arachidonoylglycerol are altered by activation of reward processes. However, the intrinsic activity of the endocannabinoid system does not appear to play a facilitatory role in brain stimulation reward and some evidence suggests it may even oppose it. The influence of the endocannabinoid system on brain reward processes may depend on the degree of activation of the different brain areas involved and might represent a mechanism for fine-tuning dopaminergic activity. Although involvement of the various components of the endocannabinoid system may differ depending on the type of rewarding event investigated, this system appears to play a major role in modulating reward processes. .

The ScienceofMarijuana
Leslie L. Iversen
2000 by Oxford University Press, Inc.
https://www.academia.edu/9803324/Science_of_Marijuana
Marijuana (cannabis) is among the most widely used of all psy­ choactive drugs. Despite the fact that its possession and use is illegal in most countries, cannabis is used regularly by as many
as 20 million people in the United States and Europe, and by millions more in other parts of the world. In recent years thousands of patients with acquired immunodeficiency syndrome (AIDS), multiple sclerosis, and a variety of other disabling diseases have begun to smoke marijuana illegally in the firm belief that it makes their symptoms better, despite the relative paucity of medical evidence to substantiate such belief.
The writer Stephen Jay Gould described his use of marijuana in suppressing the nausea associated with cancer treatment:
I had surgery, followed by a month of radiation, chemotherapy, more sur­ gery, and a subsequent year of additional chemotherapy. I found that I could control the less severe nausea of radiation by conventional medi­ cines. But when I started intravenous chemotherapy (Adriamycin),abso­ lutely nothing in the available arsenal of antiemetics worked at all. I was miserable and came to dread the frequent treatments with an almost per­ verse intensity.
. . . marijuana worked like a charm. I disliked the " side effect" of mental blurring (the "main effect" for recreational users), but the sheer bliss of not experiencing nausea —and then not having to fear it for all the days inter­ vening between treatments —was the greatest boost I received in all my year of treatment, and surely had a most important effect upon my even­tual cure. (Grinspoon and Bakalar, 1993)
In California as part of the 1996 election voters approved "Proposi­ tion 215," which sought to make it legal to smoke marijuana with a doctor's recommendation. During the following year "cannabis buyers clubs" were established throughout the state to provide supplies of cannabis for medicinal use. On the whole these were run by well­ intentioned people and were strictly regulated, patients were checked for identity, medical records, and doctor's diagnosis and only then were they allowed to purchase a small quantity of marijuana. In the 1998 state elections a further six states voted to permit access to medical Marijuana, and in early 1999, such laws began to be put into effect, despite opposi­tion from the federal government. .

The therapeutic potential of cannabis
Jarnail Singh and Janardhan Singh

ejbps, 2017, Volume 4, Issue 03, 139-146.
https://www.cannabisskunksense.co.uk/uploads/site-files/THERAPEUTIC_POTENTIAL_OF_CANNABIS.pdf

Medical marijuana use is controversial in the American society. While the states move to legalize marijuana for medical or recreational use, research is needed to elucidate the adverse effects and potential therapeutic benefits of marijuana therapy. This review provides the current information on potential indications, pharmacology, toxicity, and contraindications for medical cannabis. Understanding of the potential uses of cannabinoids in various medical conditions will benefit the patients and healthcare providers. Legalization of marijuana use in 21 states of the US and the district of Columbia has called attention for health care providers.

IC Terpenes
Beta-caryophyllene attenuates short-term recurrent seizure activity and blood-brain-barrier breakdown after pilocarpine-induced status epilepticus in rats

Michele Pereira Mallmann, Fernanda Kulinski Mello, Bruna Neuberger, Karine Gabriela da Costa Sobral, Michele Rechia Fighera, Luiz Fernando Freire Royes, Ana Flávia Furian, Mauro Schneider Oliveira
Brain Res. 2022 Mar 14;1784:147883.
doi: 10.1016/j.brainres.2022.147883.
Background: Status epilepticus (SE) is a neurological life-threatening condition, resulting from the failure of the mechanisms responsible for seizure termination. SE is often pharmacoresistant and associated with significant morbidity and mortality. Hence, ceasing or attenuating SE and its consequences is of fundamental importance. Beta-caryophyllene is a functional CB2 receptor agonist and exhibit a good safety profile. Besides, it displays beneficial effects in several experimental conditions, including neuroprotective activity. In the present study we aimed to investigate the effects of beta-caryophyllene on pilocarpine-induced SE.
Methods: Wistar rats were submitted to pilocarpine-induced SE and monitored for 24 h by video and EEG for short-term recurrence of seizure activity (i.e. seizures occurring within 24 h after termination of SE). Rats received beta-caryophyllene (100 mg/kg, ip) at 1, 8- and 16-hours after SE. Twenty-four hours after SE we evaluated sensorimotor response, neuronal damage (fluoro jade C staining) and serum albumin infiltration into brain parenchyma.

EVERY NEW PAPER I ADD FROM NOW ON I WILL FIRST POST THEM LIKE THIS SO FOLKS CAN SEE THEM AND FIND THEM EASY IN EACH CATEGORY AS THEY ARE ALSO POSTED ALPHABETICALLY IN THE MAIN ICBIB CATEGORIES. -SamS
 
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Lost Guy

Member
I will add this one also:

IC Cannabis Botany

Cryopreservation of 13 Commercial Cannabis sativa Genotypes Using In Vitro Nodal Explants

Cassandra D. Downey, Gregory Golenia, Ekaterina A. Boudko and Andrew Maxwell P. Jones
Plants 2021, 10, 1794.
DOI: 10.3390/ plants10091794
https://mdpi-res.com/d_attachment/pl...0-01794-v2.pdf
Cannabis has developed into a multi-billion-dollar industry that relies on clonal prop- agation of elite genetics with desirable agronomic and chemical phenotypes. While the goal of clonal propagation is to produce genetically uniform plants, somatic mutations can accumulate during growth and compromise long-term genetic fidelity. Cryopreservation is a process in which tissues are stored at cryogenic temperatures, halting cell division and metabolic processes to facilitate high fidelity germplasm preservation. In this study, a series of experiments were conducted to optimize various stages of cryopreservation and develop a protocol for long-term germplasm storage of Cannabis sativa. The resulting protocol uses a standard vitrification procedure to cryopreserve nodal explants from in vitro shoots as follows: nodes were cultured for 17 h in a pre-culture solution (PCS), followed by a 20-min treatment in a loading solution (LS), and a 60 min incubation in plant vitrification solution 2 (PVS2). The nodes were then flash frozen in liquid nitrogen, re-warmed in an unloading solution at 40 ◦C, and cultured on basal MS culture medium in the dark for 5 days followed by transfer to standard culture conditions. This protocol was tested across 13 genotypes to assess the genotypic variability. The protocol was successful across all 13 genotypes, but significant variation was observed in tissue survival (43.3–80%) and regrowth of shoots (26.7–66.7%). Plants grown from cryopreserved samples were morphologically and chemically similar to control plants for most major traits, but some differences were observed in the minor cannabinoid and terpene profiles. While further improvements are likely possible, this study provides a functional cryopreservation system that works across multiple commercial genotypes for long-term germplasm preservation.
 

Sam_Skunkman

"RESIN BREEDER"
Moderator
Veteran
I am back and I added the 29 papers that I could not add when I was LOST GUY.

Should I continue to post the newly added papers here at the end, so folks can find new papers quickly under
the correct section category, the individual categories have the articles alphabetised so if you know the category finding a paper is easy.
-SamS
 
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bsgospel

Bat Macumba
Veteran
It may not be necessary to include the abstracts when noting new papers at the end of the thread but the titles/authors could certainly help.


I think I will include the abstracts of the new papers to be added here at the end of the thread, it is easier for me and I think it helps people decide what to look up, sometimes titles are just not clear enough.
-SamS
 
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Sam_Skunkman

"RESIN BREEDER"
Moderator
Veteran
41 New articles added to IC BIB WWW

2 in IC Cannabinoid Receptors
2 in IC Cannabinoids
2 in IC Cannabinoids
4 in IC Cannabis Botany

1 in IC DNA
1 in IC Hemp/Cannabis Cultivation
6 in IC Legal
9 in IC Medical Cannabis/Endocannabinoids Pt 1 A-D
13 in IC Medical Cannabis/Endocannabinoids Pt 2 E-Z
1 in I
C Terpenes

-SamS



Posted in IC BIB WWW April 11 2022 .
41 New articles added to IC BIB WWW ..


IC Cannabinoid Receptors 2 .

Cannabinoid Type 2 Receptor Activation Reduces

the Progression of Kidney Fibrosis Using a Mouse
Model of Unilateral Ureteral Obstruction
Mallory L. Swanson, Kevin R. Regner, Bob M. Moore II, and Frank Park Cannabis and Cannabinoid Research Volume X, Number X, 2022
DOI: 10.1089/can.2021.0127
Background: Kidney fibrosis is a hallmark consequence of all forms of chronic kidney disease with few available treatment modalities.
Material and Methods: In this study, we performed the unilateral ureteral obstruction (UUO) procedure to investigate the effects of a selective cannabinoid type 2 (CB2) agonist receptor, SMM-295, as a nephroprotective therapy.
Results: SMM-295 was demonstrated to exhibit 50-fold selectivity over the cannabinoid type 1 (CB1) receptor with an EC50 *2 nM. Four other off-targets were identified in the safety panel, but only at the highest concentration (5 mM) tested in the assay demonstrating the relative selectivity and safety of our compound. Administration of SMM-295 (12 mg/kg IP daily) in UUO mice led to a significant decrease of 33% in tubular damage compared to the vehicle-treated UUO mice after 7 days. Consistent with these findings, there was a significant decrease in a-smooth muscle actin and fibronectin, which are markers of tubulointerstitial fibrosis, as determined by Western blot analysis. DNA damage as detected by a classic marker, c-H2AX, was significantly reduced by 50% in the SMM-295 treatment group compared to vehicle treatment. Genetic knockout of CB2 or administration of a CB2 inverse agonist did not exhibit any beneficial effect on tubulointerstitial fibrosis or kidney tubule injury.
Conclusions: In conclusion, our study provides new evidence that SMM-295 can therapeutically target the CB2 receptor with few, if any, physiological off-target sites to reduce kidney tissue damage and slow the fibrotic progression in a mouse model of kidney fibrosis.
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Peripheral, but not central effects of cannabidiol derivatives: Mediation by CB1 and unidentified receptors
Ester Fride, Datta Ponde, Aviva Breuer, Lumir Hanus
Neuropharmacology 48 (2005) 1117e1129
doi:10.1016/j.neuropharm.2005.01.023
https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.180.5931&r ep=rep1&type=pdf
Delta-9 tetrahydrocannabinol (D9-THC) and (-)-cannabidiol ((-)-CBD) are major constituents of the Cannabis sativa plant with different pharmacological profiles: (D9-THC activates cannabinoid CB1 and CB2 receptors and induces psychoactive and peripheral effects. ()-CBD possesses no, or very weak affinity for these receptors. We tested a series of (+)- and ()-CBD derivatives for central and peripheral effects in mice. None of the ()-CBD derivatives were centrally active, yet most inhibited intestinal motility.
Of the five (C)-CBD derivatives, all with CB1 receptor affinity, only (+)-7-OH-CBD-DMH (DMHZ1,1-dimethylheptyl), acted centrally, while all five arrested defecation. The effects of (+)-CBD-DMH and (+)-7-OH-CBD-DMH were inhibited by the CB1 receptor antagonist SR141716. The CB2 receptor antagonist SR144528, and the vanilloid TRPV1 receptor antagonist capsazepine, had no influence. Further, the (=)-CBD derivatives (-)-7-COOH-CBD and (-)-7-COOH-CBD-DMH, displayed anti-inflammatory activity. We suggest that (+)-CBD analogues have mixed agonist/antagonist activity in the brain. Second, ()-CBD analogues which are devoid of cannabinoid receptor affinity but which inhibit intestinal motility, suggest the existence of a non-non-CB1, non-CB2 receptor.
Therefore, such analogues should be further developed as antidiarrheal and/or antiinflammatory drugs. We propose to study the therapeutic potential of (-)- and (+)-CBD derivatives for complex conditions such as inflammatory bowel disease and cystic fibrosis.

IC Cannabinoids 2

Chemical ecology of Cannabis
David W. Pate
Journal of the International Hemp Association 2: 29, 32-37.
https://www.druglibrary.org/olsen/he.../iha01201.html
The production of cannabinoids and their associated terpenes in Cannabis is subject to environmental influences as well as hereditary determinants. Their biosynthesis occurs in specialized glands populating the surface of all aerial structures of the plant. These compounds apparently serve as defensive agents in a variety of antidessication, antimicrobial, antifeedant and UV-B pigmentation roles. In addition, the more intense ambient UV-B of the tropics, in combination with the UV-B lability of cannabidiol, may have influenced the evolution of an alternative biogenetic route from cannabigerol to tetrahydrocannabinol in some varieties.
Link but no PDF

Delta-9-Tetrahydrocannabinolic Acid B: A Mechanism for its Formation in Cannabis
Crist N. Filer Cannabis and Cannabinoid Research Volume X, Number X, 2022
DOI: 10.1089/can.2021.0216
There appears to be consensus among Cannabis biologists that delta-9-tetrahydrocannabinolic acid A (THCA-A) is the exclusive product of the enzyme THCA synthase. This then leaves an open question for formation of the THCA-A structural isomer, delta-9-tetrahydrocannabinolic acid B (THCA-B), discovered as a minor product in Cannabis in 1969. With no reasonable biochemical pathway to explain the presence of THCA-B in Cannabis, a synthetic route was next considered. Using established literature precedent, a photochemical mechanism has been proposed for the conversion of THCA-A to cannabidiolic acid (CBDA), followed by conversion of CBDA to THCA-B employing bond-breaking and bond-forming reactions. Find Pdf .

IC Cannabis nAnalysis 2

A Clinical Framework for Evaluating Cannabis Product Quality and Safety

Caroline A. MacCallum, Lindsay A. Lo, Carly A. Pistawka, and Michael Boivin Cannabis and Cannabinoid Research Volume X, Number X, 2022
DOI: 10.1089/can.2021.0137
Increase in medical cannabis use, along products, warrants the need for clinicians to be knowledgeable in evaluating the quality of any cannabis product presented in clinical practice. Determining whether a product is regulated within the region is key in assessing overall quality and safety. Regulated products are held to a higher standard including independent testing, contamination mitigation, and concentration limits. Here, we present a clinical framework in evaluating cannabis products to ascertain the quality and regulation level of the product. Evaluation includes assessing the source company, reviewing product details (e.g., type, cannabinoid content, and labeling), and assessing quality control variables such as manufacturing and decontamination processes. The quality of products patients use is an important part of mitigating cannabis-related harms, especially in medically vulnerable patients. Currently, there is a great need to implement widespread standardization and regulations to ensure product quality and safety.
Find Pdf .

Pesticide Analysis at Pace

Lauren Robertson | 03/31/2022 | Interview
https://thecannabisscientist.com/testing-processing/pesticide-analysis-at-pace
Application chemist Kirk Jensen tells us how a low-pressure gas chromatography kit and short collision cell technology helped him measure 244 pesticides in 11 minutes

Speed is king in the world of pesticide analysis; as many lab managers know, being able to process more samples in a shorter time frame – while maintaining data quality – can be invaluable in high-throughput applications. Current gas chromatography-tandem mass spectrometry (GC-MS/MS) methods are certainly sensitive, but they require longer analysis times to effectively separate complex mixtures. Feeling the need for speed, Kirk Jensen, Robert “Chip” Cody, and John Dane from JEOL decided to test an approach using a low-pressure GC (LPGC) kit (Restek) with the enhanced selected reaction monitoring (SRM) switching speed of the short collision cell in a GC-triple quadrupole MS system (JMS-TQ4000GC, JEOL)
The result? Three transitions for each of 244 pesticides were measured in a standard mixture in just 11 minutes. We spoke to Kirk Jensen to find out a little more about his work.

IC Cannabis Botany 4 .
Cannabinoid–hormone interactions in the regulation of motivational processes
Hassan H. LópezHormones and Behavior 58 (2010) 100–110

doi:10.1016/j.yhbeh.2009.10.005 https://d1wqtxts1xzle7.cloudfront.ne...ne%3B+filename %3DCannabinoid_hormone_interac tions_in_the.pdf&Expires=16488 46795&Signature=M6uyVrfsBxCNVQ X7Rn83jlahHuNeeggboBMUGOc-QmKt034vtUmssSJBYdOCUkK-YIZZhE~Z44rLDEkk8G7YrmnQJMXVnP hXBVQksS8m80EjtSzcIK8In3pRUkRu x85IB7wscY5bnRF5QHquW6Dct~8wQo m6jw6uRxmWkZKzeC89MAfZ~dBRslif hA51Pzrgdw6215fQx23tPvWGddB7fd FZsLZXtELqWC9uLkK4dfu0U81FMBqg wtU2FQBtbrVjO93D3e9vFX3RjWfSw2 yHf8FlSSBifv2k-NT2NqUIS5RR4W2je1VBQWDSr4g-sr~a0GNfWT-5sd0qb1PBdY65gg__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA
There is a bi-directionality in hormone–cannabinoid interactions: cannabinoids affect prominent endocrine axes (such as the hypothalamic–pituitary–gonadal ), and gonadal hormones modulate cannabinoid effects. This review will summarize recent research on these interactions, with a specific focus upon their implications for motivated behavior. Sexual behavior will serve as a “case study.” I will explore the hypothesis that ovarian hormones, in particular estradiol, may serve to release estrous behavior from endocannabinoid inhibition. Hormonal regulation of the endogenous cannabinoid system also affects processes that underlie drug abuse. This review will briefly discuss sex differences in behavioral responses to cannabinoids and explore potential mechanisms by which gonadal hormones alter cannabinoid reward. An examination of this research informs our perspective on how hormones and endocannabinoids may affect drug-seeking behavior as a whole and the development of addiction

Cannabis Indoor Growing Conditions, Management Practices, and Post-Harvest Treatment: A Review
Dan Jin, Shengxi Jin, Jie Chen
American Journal of Plant Sciences, 2019, 10, 925-946
DOI: 10.4236/ajps.2019.106067
https://www.scirp.org/pdf/AJPS_2019061713561499.pdf
Cannabis has attracted a new wave of research attention as an herbal medicine. To deliver compliant, uniform, and safe cannabis medicine, growers should optimize growing environments on a site-specific basis. Considering that environmental factors are interconnected, changes in a factor prompts adjustment of other factors. This paper reviews existing work that considers indoor growing conditions (light, temperature, CO2 concentration, humidity, growing media, and nutrient supply), management practices (irrigation, fertilization, pruning & training, and harvest timing), and post-harvest treatment (drying and storage) for cannabis indoor production.

Cannabis, the multibillion dollar plant that no genebank wanted
Davoud Torkamaneh and Andrew Maxwell Phineas Jones
Genome Volume 65, Number 1, January 2022
https://cdnsciencepub.com/doi/10.1139/gen-2021-0016
Although cannabis is legalized and accepted as an agricultural commodity in many places around the world, a significant lack of public germplasm repositories remains an unresolved problem in the cannabis industry. The acquisition, preservation, and evaluation of germplasm, including landraces and ancestral populations, is key to unleashing the full potential of cannabis in the global marketplace. We argue here that accessible germplasm resources are crucial for long-term economic viability, preserving genetic diversity, breeding, innovation, and long-term sustainability of the crop. We believe that cannabis restrictions require a second look to allow genebanks to play a fuller and more effective role in conservation, sustainable use, and exchange of cannabis genetic resources.

Cryopreservation of 13 Commercial Cannabis sativa Genotypes Using In Vitro Nodal Explants
Cassandra D. Downey, Gregory Golenia, Ekaterina A. Boudko and Andrew Maxwell P. Jones
Plants 2021, 10, 1794.
DOI: 10.3390/ plants10091794
https://mdpi-res.com/d_attachment/pl...0-01794-v2.pdf
Cannabis has developed into a multi-billion-dollar industry that relies on clonal prop- agation of elite genetics with desirable agronomic and chemical phenotypes. While the goal of clonal propagation is to produce genetically uniform plants, somatic mutations can accumulate during growth and compromise long-term genetic fidelity. Cryopreservation is a process in which tissues are stored at cryogenic temperatures, halting cell division and metabolic processes to facilitate high fidelity germplasm preservation. In this study, a series of experiments were conducted to optimize various stages of cryopreservation and develop a protocol for long-term germplasm storage of Cannabis sativa. The resulting protocol uses a standard vitrification procedure to cryopreserve nodal explants from in vitro shoots as follows: nodes were cultured for 17 h in a pre-culture solution (PCS), followed by a 20-min treatment in a loading solution (LS), and a 60 min incubation in plant vitrification solution 2 (PVS2). The nodes were then flash frozen in liquid nitrogen, re-warmed in an unloading solution at 40 C, and cultured on basal MS culture medium in the dark for 5 days followed by transfer to standard culture conditions. This protocol was tested across 13 genotypes to assess the genotypic variability. The protocol was successful across all 13 genotypes, but significant variation was observed in tissue survival (43.3–80%) and regrowth of shoots (26.7–66.7%). Plants grown from cryopreserved samples were morphologically and chemically similar to control plants for most major traits, but some differences were observed in the minor cannabinoid and terpene profiles. While further improvements are likely possible, this study provides a functional cryopreservation system that works across multiple commercial genotypes for long-term germplasm preservation.

IC DNA 1

Genome-Wide Identification and Expression Profiles
of bZIP Genes in Cannabis sativa L.
Meng Lu, Xiang-Xiao Meng, Yi-Ming Zhang, Xue-Wen Zhu, Jun Li, Wei-Qiang Chen, Hui-Hua Wan, Si-Fan Wang, Xue Cao, Wei Sun, Yao-Lei Mi, and Jun-Wen Zhai
Cannabis and Cannabinoid Research Volume X, Number X, 2022
DOI: 10.1089/can.2021.0153
Background: The bZIP gene family plays roles in biotic and abiotic stress, secondary metabolism, and other aspects in plants. They have been reported in Arabidopsis thaliana, Oryza sativa, Artemisia annua, and other plants, but their roles in Cannabis sativa have not been determined.

Materials and Methods: In this study, we analyzed the genome-wide identification and expression profile of the bZIP gene family in C. sativa.
Results: A total of 51 members of the bZIP gene family were identified based on the C. sativa genome and numbered in order from CsbZIP1 to CsbZIP51. Their phylogenetic relationships, cis-elements in promoter region, gene structures and motif compositions, physicochemical properties, chromosome locations, and expression profiles, were analyzed. The results showed that the 51 CsbZIPs were unevenly distributed on 10 chromosomes and could be clustered into 11 subfamilies. Furthermore, CsbZIPs located in the same subfamilies presented similar intron/exon organization and motif composition. The expression levels of CsbZIPs in various tissues (flowers, bracts, vegetative leaves, stems, and seeds) were determined using reverse transcription quantitative polymerase chain reaction. The expression levels of CsbZIPs were higher in flowers and bracts. The 51 CsbZIPs were explored, and their structure, evolution, and expression pattern in different tissues of C. sativa were characterized synthetically. The findings indicated that CsbZIPs are essential for the growth and development of C. sativa.
Conclusions: These results provide a theoretical basis for subsequent research on hemp bZIP transcription factors and the cultivation of high-cannabidiol and low-tetrahydrocannabinol high-quality cannabis varieties.
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IC Hemp/Cannabis Cultivation 1

Impact of varying plant densities on two industrial hemp cultivars grown in the Manawatu
Q.M. Swanepoel, R. Barge, E. Kawana-Brown3and L.H.J Kerckhoffs
Agronomy New Zealand 48, 2018
https://www.agronomysociety.org.nz/f...ty_effects.pdf
Industrial hemp (Cannabis sativa L) is a fast-growing annual multi-purpose crop grown for its fibres, hurd, seeds and pharmaceuticals. The commercial production of industrial hemp is strictly legislated and only approved cultivars with delta-9-tetrahydrocannibinol (THC) levels under 0.35% are permitted in New Zealand. The effect of varying plant densities was studied for two industrial hemp cultivars (Fasamo and Ferimon 12) in the Manawatu region. Four planting densities (40, 80, 120 and 160 plants/m2 ) at two row spacings (15 cm and 30 cm) were evaluated. Ferimon 12 produced the greatest average biomass of 34.6 t/ha with 160 plants/m2 at a 30 cm row spacing. Cultivar not plant density or row spacing had the most effect on agronomic measurements. Ferimon 12 produced longer, heavier stems with higher overall biomass compared to Fasamo regardless of plant density or row spacing. Individual stem weight decreased as plant population increased for both cultivars. Higher planting density and closer row spacing improved weed suppression. .

IC Legal 6 .

Declared Rationale for Cannabis Use Before and After Legalization for Nonmedical Use: A Longitudinal Study of Community Adults in Ontario

Mahmood AminiLari, Jason W. Busse, Jasmine Turna, and James MacKillop
https://www.researchgate.net/publication/359486690_Declared_Rationale_f or_Cannabis_Use_Before_and_Aft er_Legalization_for_Nonmedical _Use_A_Longitudinal_Study_of_C ommunity_Adults_in_Ontario
https://www.liebertpub.com/doi/10.10...rid:crossref.o rg&rfr_dat=cr_pub%20%200pubme d

Objectives: To examine the proportion of individuals using cannabis for medical purposes who reported nonmedical use of cannabis after it became legal to do so.
Materials and Methods: We acquired data from the Population Assessment for Tomorrow’s Health, the Cannabis Legalization Surveillance Study on a subpopulation of participants residing in Hamilton, Ontario, Canada, who
reported using cannabis for medical purposes. Specifically, we acquired data 6 months before, and again 6 months after, legalization of cannabis for nonmedical purposes. We constructed a logistic regression model to explore the association between potential explanatory factors and endorsing exclusively nonmedical use after legalization and reported associations as odds ratios and 95% confidence intervals.
Results: Our sample included 254 respondents (mean age 33 – 13; 61% female), of which 208 (82%) reported both medical and nonmedical use of cannabis (dual motives) before legalization for nonmedical purposes, and 46 (18%) reported cannabis use exclusively for medical purposes. Twenty-five percent (n = 63) indicated they had medical authorization to use medical cannabis, of which 37 (59%) also endorsed nonmedical use. After legalization of nonmedical cannabis,*1 in 4 previously exclusive cannabis users for medical purposes declared dual use (medical and nonmedical), and *1 in 4 previously dual users declared exclusively nonmedical use of cannabis. No individual with medical authorization reported a change to exclusively nonmedical use after legalization. Our adjusted regression analysis found that younger age, male sex, and lacking authorization for cannabis use were associated with declaring exclusively nonmedical use of cannabis after legalization. Anxiety, depression, impaired sleep, pain, and headaches were among the most common complaints for which respondents used cannabis therapeutically. Most respondents reported using cannabis as a substitute for prescription medication at least some of the time, and approximately half reported using cannabis as a substitute for alcohol at least some of the time.
Conclusions: In a community sample of Canadian adults reporting use of cannabis for medical purposes, legalization of nonmedical cannabis was associated with a substantial proportion changing to either dual use (using cannabis for both medical and nonmedical purposes) or exclusively nonmedical use. Younger men without medical authorization for cannabis use were more likely to declare exclusively nonmedical use after legalization.
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International Drug Control and Human rights: Mounting tensions or innovative convergence?
Karen Mamo
Academia Letters, Article 2667. (2021)
DOI: 10.20935/AL2667

www.academia.edu/50968955/International_Drug_Control_and _Human_righys_Mounting_trnsion s_or_innobative_convergence
The World Drug Report 2020 highlights that global figures for illicit drug use continued to increase and in 2018 reached 269 million users. This is in stark difference to the number of drug users in the early 2000’s, with the World Drug Report of 2002 estimating 185 million drug users. Interestingly, the World Drug Report 2020 highlights that although prevalence of use is most common in developed and rich countries, it is poor and developing states that carry the heaviest burden of problematic substance use and problems. (World Drug Report, 2002) (World Drug Report, 2020) Some countries, such as Uruguay, fully regulating the consumption, cultivation and sale of the non-medical use of cannabis in 2013, argue that a similar legislative and paradigm shift is based on the recognition that the criminal approach has been causing a number of ‘unintended consequences’ and that principles of human rights and public health prevail on the criminalised aspect required by the UN Drug Control Conventions. (Ramsey, 2016) In the past ten years, various countries in Europe, the Americas, and the Caribbean, have been moving towards a less punitive approach and more towards a human rights-based drug policy. These new legislative changes have been directly challenging the status quo that has relatively dominated the international approach to address and curtail the use and trafficking of illicit substances. This situation is creating an environment of potential tensions or opportunity for innovative convergence between obligations falling under the UN Drug Control Conventions of 1961, 1977 and 1988 and those originating from International Human Rights

More than half of Europeans support cannabis legalization -report
Rithika Krishna
April 7, 2022
https://www.reuters.com/world/europe...rt-2022-04-07/
More than half of the European population support legalization of adult use of cannabis and around 30% of them are interested in purchasing it, according to polling data by industry consultants on Thursday.
Europe's liberal approach could reap multiple financial and economic benefits as seen in the United States, which has witnessed a surge in cannabis use during pandemic-induced lockdowns.
While majority of Europeans support regulated cannabis shops, most do not favor growing the plant at home, according to the report by London-based consultancy Hanway and pot producer Curaleaf International.
The report comes a week after the U.S. House of Representatives on Friday passed a bill to end the federal ban on marijuana, which has created legal headaches for users and businesses in the states that have legalized it.
"We see the European market as three to four years behind (the U.S.), but it actually looks like Europe may initiate sweeping reform before the United States," said Boris Jordan, executive at U.S.-based Curaleaf.
Many European countries, including Germany, have legalized cannabis for limited medicinal purposes, while others have decriminalized its general use. Malta became the first European country to allow limited cultivation and personal use of cannabis. read more
The European cannabis market is expected to cross 3 billion euros ($3.27 billion) in annual revenue by 2025, up from about 400 million euros last year, according to a report from research firm Prohibition Partners. Germany has been the biggest market in the continent so far.
"There is clear political desire and willingness in Germany to legalize recreational use," Joe Bayern, chief executive officer of Curaleaf, told Reuters.
"Given it (Germany) is the largest economy in Europe, we think it will lead the way and create a domino effect for rest of the continent," Bayern said.

Prices and Purchase Sources for Dried Cannabis Flower in the United States, 2019–2020
Elle Wadsworth, Pete Driezen, Rosalie Liccardo Pacula, Beau Kilmer, and David Hammond
Cannabis and Cannabinoid Research Volume X, Number X, 2022

DOI: 10.1089/can.2021.0232
Introduction: The price of cannabis has major implications for public health, public safety, social equity, and government revenues. This article examines prices and sources of purchased dried cannabis flower among consumers
facing different state laws in the United States.
Methods: Repeat cross-sectional survey data were collected from the International Cannabis Policy Study in 2019 and 2020. U.S. respondents were recruited through online commercial panels, ages 16–65, and purchased
dried flower in the past year (n = 9766). Weighted binary logistic regression models examined legal purchasing in states that had legalized recreational cannabis.
Results: Compared with respondents in states with recreational stores, respondents living in ‘‘illegal,’’ ‘‘medical,’’ and ‘‘recreational’’ states without stores were associated with paying a higher unit price of dried flower ( + 20.5%, + 23.6%, + 27.4%, respectively; all p < 0.05). The majority of respondents in states with recreational stores last purchased from stores/dispensaries (2019: 66.6%; 2020: 62.0%) and the odds of purchasing legally was greater with each additional year after stores opened (adjusted odds ratio = 1.48, 95% confidence interval: 1.37, 1.60).
Conclusions: Cannabis prices and purchase behaviors are strongly influenced by its legal status and presence of stores. After states legalize for recreational purposes, it takes multiple years for the legal market to become established
as the number of retail stores increase and prices decrease. The findings demonstrate that consumers use sources that they are legally allowed to access, suggesting an increased number of physical retail stores and online delivery services could expand uptake of legal sources in states with recreational cannabis laws. Find Pdf

Status and Impacts of Recreational and Medicinal Cannabis Policies in Africa: A Systematic Review and Thematic Analysis of Published and ‘‘Gray’’ Literature
Chenai Kitchen, John Alimamy Kabba, and Yu Fang
Cannabis and Cannabinoid Research Volume X, Number X, 2022

DOI: 10.1089/can.2021.0110
Background: Despite cannabis’s societal ubiquity, several African states remain traditional prohibitionists. However, cannabis is becoming a more explored frontier from a health, human rights, and monetary perspective. A number of African countries have taken to tailoring their policies to better engage in emerging global dialogs. Nevertheless, the focus is majorly on the crop’s financial appeal with less consideration on impacts of policies. This review aimed to specifically focus on the identification of existing or pending policies, indicating national positioning in terms of recreational and medicinal cannabis use and summarizing publications addressing related impacts in Africa.
Methods: We systematically searched six academic research databases (including Google Scholar), Google, country specific websites, and websites of relevant organizations. Included publications were in English and published between January 1, 2000, and November 31, 2020 (with exception granted to official legislation not in
English and/or published earlier than 2000, but still in effect). Reference lists of included publications were screened for potentially relevant publications. Results were synthesized thematically and descriptively.
Results: Cannabis is Africa’s most consumed illegal substance, its use entrenched in social, political, historical, economic, and medicinal ties. African users constitute a third of the worldly total and cultivation is a major activity. Policies have led to prison overcrowding, accelerated environmental damage, and sourced regional instability.
South Africa, Seychelles, and Ghana have decriminalized personal use with Egypt and Mozambique exploring similar legislation. Eleven countries have existing or pending medicinal cannabis-specific provisions. South Africa and Seychelles stand out as having regulations for patients to access medicinal cannabis. Other countries have made provisions geared toward creating export markets and economic diversification.
Conclusion: Cannabis policy is a composite and complex issue. Official stances taken are based on long withstanding narratives and characterized by a range of contributing factors. Policy changes based on modern trends should include larger studies of previous policy impacts and future-oriented analysis of country-level goals incorporated with a greater understanding of public opinion.
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The Rise and Decline of Cannabis Prohibition the History of cannabis in the UN drug control system and options for reform
Dave Bewley-Taylor, Tom Blickman, Martin Jelsma
TRANSNATIONAL I N S T I T U T E March 2014
https://www.tni.org/files/download/r...ecline_web.pdf
Cannabis has long been a substance drawing much attention within the international drug control regime, a system currently based upon the 1961 Single Convention on Narcotic Drugs. Today the regime landscape is changing. Faced with particular challenges and democratic decisions, a number of jurisdictions are moving beyond merely tolerant approaches to the possession of cannabis for personal use to legally regulating markets for the drug. In November 2012 voters within the U.S. states of Colorado and Washington passed ballot initiatives to tax and regulate cannabis cultivation, distribution and consumption for non-medical purposes. Just over a year later, Uruguay legislated state regulation of the entire chain of the domestic cannabis market for medical, industrial and recreational use. These policy shifts go well beyond the permitted prohibitive boundaries of the UN drug control conventions. They represent a break with an historical trajectory founded on dubious science and political imperatives. And they have thrown the global regime into a state of crisis, as this report will argue. This publication is a joint effort of the Transnational Institute in Amsterdam and the Global Drug Policy Observatory at Swansea University. Research has been going on in various stages for about two years, and interim results were presented at the Seventh Annual Conference of the International Society for the Study of Drug Policy at the Universidad de los Andes, in Bogotá, in May 2013 and further discussed in an expert seminar on cannabis regulation in October 2013 in Amsterdam. Many academics, government officials and experts from NGOs and international agencies have provided useful comments on earlier drafts, but needless to say the end result is the sole responsibility of the authors. This final report will be first presented at the 57th session of the UN Commission on Narcotic Drugs (CND) in Vienna, 13-21 March 2014.

IC Medical Cannabis/Endocannabinoids Pt 1 A-D 9

Analysis of 2-Arachidonoylglycerol Levels in Polycystic Ovary Syndrome in the Context of Hormonal and Metabolic Alterations and Across the Classical Phenotypes

Plamena Kabakchieva, Antoaneta Gateva, Julieta Hristova, Tsvetoslav Georgiev, and Zdravko Kamenov Cannabis and Cannabinoid Research Volume X, Number X, 2022
DOI: 10.1089/can.2021.0183
Introduction: Ovarian folliculogenesis requires a fine balance between extra- and intra-ovarian factors. Endocannabinoids are found in the female reproductive system and are essential for a normal follicular growing process and ovulation. First, our study aimed to analyze levels of the endocannabinoid—2-arachidonoylglycerol (2-AG)— in patients with polycystic ovary syndrome (PCOS) and to compare with healthy controls. In addition, the study aimed to explore the association of 2-AG with hormonal and metabolic alterations, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) across the classical PCOS phenotypes.
Methods: Fifty-four women with PCOS were compared with 26 healthy controls. PCOS patients were diagnosed and phenotyped according to the Rotterdam criteria. Further analyses were performed with the classical PCOS phenotypes A and B comprising hyperandrogenism with oligo-anovulation with or without PCOM, respectively. Full medical history, clinical investigations, anthropometric measurements, laboratory tests, and ultrasound investigations were carried out in the follicular phase. Serum levels of 2-AG were measured by enzyme-linked immunosorbent assay.
Results: PCOS patients (n = 54) and healthy controls (n = 26) showed similar metabolic parameters and anthropometric characteristics. PCOS patients were more hirsute than healthy women ( p = 0.001). Luteinizing hormone/ follicle-stimulating hormone ratio and serum levels of androgens were significantly higher in the patient than in the control group ( p = 0.035, p < 0.001, respectively). Free androgen index was also higher in the patient group ( p = 0.002). Serum levels of 2-AG did not significantly differ when comparing all PCOS patients versus healthy controls; however, further analysis of individual phenotype groups revealed that 2-AG levels in PCOS patients with phenotyope A (n = 30) were significantly lower when compared with PCOS patients with phenotype B (n = 20) and healthy controls (n = 26).
Conclusion: Serum levels of 2-AG were similar between PCOS patients and healthy controls. Nevertheless, phenotype A PCOS patients had significantly lower levels of the endocannabinoid compared with phenotype B patients
and healthy controls. Collectively, these results suggest that overall serum levels of 2-AG are not a diagnostic marker for PCOS; however, their altered secretion or activity may influence normal follicular processes.
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Arrhythmic Effects of Cannabis in Ischemic Heart Disease

Leah Gillett, Cecelia Johnson-Sasso, Brian Miller, Courtney Shakowski, Lori A. Walker, and Christine Tompkins,
Cannabis and Cannabinoid Research Volume X, Number X, 2022

DOI: 10.1089/can.2021.0188
Rationale: Cannabis use is increasing worldwide, especially among older individuals at risk for chronic ischemic heart disease (IHD). However, little is known about the arrhythmic effects of cannabis use in IHD. Accordingly,
we prospectively assessed the relationship between cannabis use, heart rate (HR), and arrhythmias in healthy age-matched controls and subjects with IHD.
Methods: Healthy controls (n = 37, 57% men) and subjects with IHD (myocardial infarction ‡ 3 months ago; n = 24, 58% men) who used cannabis wore a Zio_ (iRhythm Technologies) monitor for 14 days. Noncannabis
using ischemic subjects (n = 35, 51% males) wore Zio monitors for standard clinical indications. Baseline HR was compared with average HR measured for 4 h following consumption and changes in HR and frequency of arrhythmias were correlated with cannabis use.
Results: In controls, HR increased 20 min (4.99 – 6.7 bpm, p = 0.08) after use, then declined 4 h following use (_7.4 – 7.7, p < 0.001). Conversely, subjects with IHD showed minimal HR increase (1.6 – 3.9 bpm) and blunted
HR decline (_3.4 – 5.6 bpm, p < 0.001). Supraventricular tachycardia (SVT) (29.7% vs. 58.3%; p = 0.04) and nonsustained ventricular tachycardia (NSVT) (5.6% vs. 47.8%, p = 0.01) were the most frequently occurring arrhythmias in
controls and IHD subjects, respectively. Incidence of SVT decreased as cannabis use increased in both groups. Conversely, NSVT tended to increase with increased use in controls, and was significantly more prevalent in
IHD. However, overall arrhythmia burden did not differ between cannabis users and nonusers with IHD.
Conclusion: Our findings demonstrate that chronic cannabis use is associated with only mild HR changes, which are blunted in IHD. In addition, our data suggest that among cannabis users, arrhythmias are more frequent in IHD subjects that in healthy subjects .

Cannabidiol, a Regulator of Intracellular Calcium and Calpain

Kyung-Hwa Jeon, Sang-Hyuck Park, Woong Jin Bae, Sae Woong Kim, Hyo Jung Park, Soomin Kim, Tae Hyung Kim, Seung Hwan Jeon, Ilbum Park, Hyun-Je Park, and Youngjoo Kwon
Cannabis and Cannabinoid Research Volume X, Number X, 2022

DOI: 10.1089/can.2021.0197
Cannabidiol (CBD) is one of the most abundant components of Cannabis and has long been used in Cannabisbased preparations. Recently, CBD has become a promising pharmacological agent because of its beneficial properties in the pathophysiology of several diseases. Although CBD is a kind of cannabinoid and acts on cannabinoid receptors (CB1 and CB2), molecular targets involved in diverse therapeutic properties of CBD have not been identified because CBD also interacts with other molecular targets. Considering that CBD alters the intracellular calcium level by which calpain activity is controlled, and both CBD and calpain are associated with various diseases related to calcium signaling, including neurological disorders, this review provides an overview of calpain and calcium signaling as possible molecular targets of CBD. As calpain is known to play an important role in the pathophysiology of neurological disease, a deeper understanding of its relationship with CBD will be meaningful. To understand the role of CBD as a calpain regulator, in silico structural analysis on the binding mode of CBD with calpain was performed.
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Cannabidiol effects on cognition in individuals with cocaine use disorder: Exploratory results from a randomized controlled trial

Elie Rizkallah, Violaine Mongeau-Perusse, Leonardo Lamanuzzi, Sol’Abraham Castenada-Ouellet, Emmanuel Stip, Louis-Christophe Juteau, Suzanne Brissette, Julie Bruneau, Simon Dubreucq, Didier Jutras-Aswa
Pharmacology, Biochemistry and Behavior 216 (2022)
https://reader.elsevier.com/reader/s...20220411012302
Background: Cocaine use disorder (CUD) is associated with various cognitive deficits that impede patients' functionality, prognosis and therapeutic outcomes. New pharmacological treatments for CUD that could improve cognition are needed.
Objective: To explore whether cannabidiol (CBD) is superior to placebo to improve cognitive functioning in individuals with CUD.
Methods: We conducted an exploratory analysis of a single site, randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy in reducing craving, cocaine use and relapse in individuals with CUD. Seventy- eight individuals diagnosed with CUD were randomized to receive either CBD (800 mg) or placebo for 92 days. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess inhibition (Stop Signal Task; SST), risky decision making (Cambridge Gambling Task; CGT) and visual memory (Pattern Recognition Memory; PRM). This assessment was made on day 1, day 7 and at week 6. We controlled for sex, severity of dependence and baseline cognitive scores in our generalized estimating equation models.
Results: Both groups performed similarly on the PRM (correct answers: p = 0.080), SST (stop signal reaction time: p = 0.644) and CGT (quality of decision making: p = 0.994; deliberation time: p = 0.507; delay aversion: p = 0.968; risk taking: p = 0.914) tests.
Conclusions: We found no evidence for 800 mg of CBD to be more efficacious than placebo for improving cognitive outcomes. Clinical trials evaluating pharmacological treatments for CUD should continue to be a research priority

Cannabidiolinduced activation of the metallothionein pathway impedes anticancer effects of disulfiram and its metabolite CuET
Tereza Buchtova, Zdenek Skrott, Katarina Chroma, Jiri Rehulka, Petr Dzubak, Marian Hajduch, David Lukac, Stefanos Arampatzis, Jiri Bartek,and Martin Mistrik
Mol Oncol. 2022 Apr; 16(7): 1541–1554.
doi: 10.1002/1878-0261.13114
https://www.ncbi.nlm.nih.gov/pmc/art...L2-16-1541.pdf
Disulfiram (DSF), an established alcohol‐aversion drug, is a candidate for repurposing in cancer treatment. DSF’s antitumor activity is supported by preclinical studies, case reports, and small clinical trials; however, ongoing clinical trials of advanced‐stage cancer patients encounter variable results. Here, we show that one reason for the inconsistent clinical effects of DSF may reflect interference by other drugs. Using a high‐throughput screening and automated microscopy, we identify cannabidiol, an abundant component of the marijuana plant used by cancer patients to mitigate side effects of chemotherapy, as a likely cause of resistance to DSF. Mechanistically, in cancer cells, cannabidiol triggers the expression of metallothioneins providing protective effects by binding heavy metal‐based substances including the bis‐diethyldithiocarbamate‐cop per complex (CuET). CuET is the documented anticancer metabolite of DSF, and we show here that the CuET’s anticancer toxicity is effectively neutralized by metallothioneins. Overall, this work highlights an example of undesirable interference between cancer therapy and the concomitant usage of marijuana products. In contrast, we report that insufficiency of metallothioneins sensitizes cancer cells toward CuET, suggesting a potential predictive biomarker for DSF repurposing in oncology.
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Cannabis (marijuana): Psychoactive properties, Addiction, Therapeudic uses and toxicity
Sumanasekera WK and Spio KJ
Addict Behav Ther Rehabil 2016, 5:2
DOI: 10.4172/2324-9005.1000156
https://www.researchgate.net/publica...erties_Addicti on_Therapeutic_Uses_and_Toxici ty
Background and Objectives: To analyze the existing literature
on cannabis (marijuana) under several sub topics; history of use, addiction, mechanism of action, therapeutic uses, and adverse effects.
Methods: A comprehensive literature search was conducted. Data sources include original research articles, systematic reviews and meta- analysis, and web-based references such as Drug strategy monographs and Merck Index. Data bases such as PubMed and Cinhal was used. References were from 1979 -2016.
Hypothesis: Based on the available literature it can be hypothesized that despite the addictive properties and adverse effects, marijuana has a therapeutic potential and should be used with caution.
Results: The available literature on cannabis smoke was discussed under five major categories, which are history of use, addiction, mechanism of action, therapeutic uses, and adverse effects.
Discussion and Conclusions: Marijuana (preparations of the hemp plant, cannabis sativa), is usually consumed as a smoke. It is an addictive compound that has been consumed for medical ailments for generations. The mechanism of action of cannabis was not known until the recent discovery of the endocannabinoid system.
Endocannabinoids are released from the post-synaptic neurons and act on the pre-synaptic neurons. Δ-9 tetrahydrocannabinol (THC), the psychoactive component present in Cannabis behaves similar to endocannabinoids. In addition to psychoactive modulations, cannabis consumption leads to cognitive impairments. Despite its’ medicinal and recreational value, due to its’ addictive properties cannabis consumption has been banned by several countries. In US, recreational and therapeutic use of cannabis is recently allowed in some states.
Scientific Significance: Despite the psych activity associated with cannabis consumption, it can be used therapeutically for many diseases including epilepsy and to alleviate chronic neuropathic pain associated with many sicknesses. Cannabis also possesses anti-cancer properties. However, strict laws should be enforced to avoid its’ abuse while allowing its’ medicinal use..

Cannabis use, pain interference, and prescription opioid receipt among persons with HIV: a target trial emulation study

William C. Becker, Yu Li, Ellen C. Caniglia, Rachel Vickers-Smith, Termeh Feinberg, Brandon D.L. Marshall & E. Jennifer Edelman
AIDS Care Psychological and Socio-medical Aspects of AIDS/HIV
https://www.tandfonline.com/doi/abs/...nalCode=caic20
DOI: 10.1080/09540121.2021.1944597
Concomitant with expanded legalization, cannabis is increasingly used to treat chronic pain among persons with HIV (PWH), despite equivocal benefit in research limited by small sample sizes and short duration of follow-up. To address these limitations, among a sample of PWH with pain interference enrolled in the Veterans Aging Cohort Study, we performed a target trial emulation study to compare the impact of four cannabis use strategies on pain interference. Among those receiving long-term opioid therapy (LTOT), we also explored impact of these strategies on ≥ 25% LTOT dose reduction. Among the analytic sample (N = 1284), the majority were men with a mean age of 50. Approximately 31% used cannabis and 12% received LTOT at baseline. Adjusting for demographic and clinical factors, cannabis use in any of 4 longitudinal patterns was not associated with resolved pain interference over 12- to 24-month follow-up. Among 153 participants receiving LTOT at baseline, cannabis use at both baseline and followup was negatively associated with LTOT dose reduction compared to no use at both baseline and follow-up. These findings support other observational studies finding no association between cannabis use and improved chronic pain or LTOT reduction among PWH.

Classification of Various Marijuana Varieties by Raman Microscopy and Chemometrics
Luis Ramos-Guerrero, Gemma Montalvo, Marzia Cosmi, Carmen Garca-Ruiz and Fernando E. Ortega-Ojeda
Toxics2022, 10, 115.
Doi: 10.3390/ toxics10030115
https://www.mdpi.com/2305-6304/10/3/...m_medium=email
The Raman analysis of marijuana is challenging because of the sample’s easy photo- degradation caused by the laser intensity. In this study, optimization of collection parameters and laser focusing on marijuana trichome heads allowed collecting Raman spectra without damaging the samples. The Raman spectra of 9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) standard cannabinoids were compared with Raman spectra of five different types of marijuana: four Sativa varieties (Amnesia Haze, Amnesia Hy-Pro, Original Amnesia, and Y Griega) and one Indica variety (Black Domina). The results verified the presence of several common spectral bands that are useful for marijuana characterization. Results were corroborated by the quantum chemical simulated Raman spectra of their acid-form (tetrahydrocannabinol acid (THCA), cannabidiol acid (CBDA)) and decarboxylated cannabinoids (THC, CBD, and CBN). A chemometrics-assisted method based on Raman microscopy and OPLS-DA offered good classification among the different marijuana varieties allowing identification of the most significant spectral bands. .

Delta-9-Tetrahydrocannabinol, Cannabidiol, and Acute Psychotomimetic States: A Balancing Act of the Principal Phyto-Cannabinoids on Human Brain and Behavior

Suhas Ganesh, Jose Cortes-Briones, Ashley M. Schnakenberg Martin, Patrick D. Skosnik, Deepak C. D’Souza, and Mohini Ranganathan,
Cannabis and Cannabinoid Research Volume X, Number X, 2022

DOI: 10.1089/can.2021.0166
Background: THC and CBD are the principal phyto-cannabinoids in the cannabis plant. The differential and possibly antagonistic effects of these compounds on specific brain and behavioral responses, and the mechanisms
underlying their effects have generated extensive interest in pre-clinical and clinical neuroscience investigations.
Methods: In this double-blind randomized placebo-controlled counterbalanced Human Laboratory Study, we examined the effects of three different dose ratios of CBD:THC (1:1, 2:1, and 3:1) on ‘‘neural noise,’’ an electrophysiological biomarker of psychosis known to be sensitive to cannabinoids as well as subjective and psychotomimetic effects. Healthy volunteers (n = 28, 12 women) with at least one prior exposure to cannabis participated in the study.
Outcomes: The lowest CBD (2.5 mg):THC (0.035 mg/kg) ratio (1:1) resulted in maximal attenuation of both THC induced psychotomimetic effects (Positive and Negative Syndrome Scale [PANSS] positive: Anova Type Statistic [ATS] = 7.83, pcorrected = 0.015) and neural noise (ATS = 8.83, pcorrected = 0.009). Further addition of CBD did not reduce the subjective experience of THC-induced ‘‘high’’ ( p > 0.05 for all CBD doses).
Interpretation: These novel results demonstrate that CBD attenuates specific THC-induced subjective and objective effects relevant to psychosis in a dose/ratio-dependent manner. Given the increasing global trend of cannabis liberalization and application for medical indications, these results assume considerable significance given the potential dose-related interactions of these key phyto-cannabinoids. Trial registration: The trial was registered in clinicaltrials.gov ID: NCT01180374.
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IC Medical Cannabis/Endocannabinoids Pt 2 E-Z 13


Endocannabinoid signaling in brain diseases: Emerging revelance of glial cells
Ana Bernal-Chico, Vanja Tepavcevic, Andrea Manterola, Carmen Utrilla, Carlos Matute, Susana Mato Glia.
Glia
. 2022;1–24.
DOI: 10.1002/glia.24172

https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24172
The discovery of cannabinoid receptors as the primary molecular targets of psychotropic cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) in late 1980s paved the way for investigations on the effects of cannabis-based therapeutics in brain pathology. Ever since, a wealth of results obtained from studies on human tissue samples and animal models have highlighted a promising therapeutic potential of cannabinoids and endocannabinoids in a variety of neurological disorders. However, clinical success has been limited and major questions concerning endocannabinoid signaling need to be satisfactorily addressed, particularly with regard to their role as modulators of glial cells in neurodegenerative diseases. Indeed, recent studies have brought into the limelight diverse, often unexpected functions of astrocytes, oligodendrocytes,
and microglia in brain injury and disease, thus providing scientific basis for targeting glial cells to treat brain disorders. This Review summarizes the current knowledge on the molecular and cellular hallmarks of endocannabinoid signaling in glial cells and its clinical relevance in neurodegenerative and chronic inflammatory disorders.

Endometriosis and Cannabis Consumption During the COVID-19 Pandemic: An International Cross-Sectional Survey
Mike Armour, Justin Sinclair, Junipearl Cheng, Preston Davis, Aaish Hameed, Harini Meegahapola, Krithika Rajashekar, Sunethra Suresh, Andrew Proudfoot, and Mathew Leonardi
Cannabis and Cannabinoid Research Volume X, Number X, 2022

DOI: 10.1089/can.2021.0162
Introduction: Endometriosis affects 1 in 10 women worldwide, with most experiencing difficulties achieving adequate symptom control. These difficulties have been compounded by the onset of the COVID-19 pandemic
due to worldwide shifts in health care resource allocation. As cannabis is a relatively common form of selfmanagement in endometriosis, this study aims to explore the impact of the COVID-19 pandemic on cannabis consumption in those with endometriosis.
Methods: An anonymous, cross-sectional online international survey was developed and promoted by endometriosis advocacy/support organizations worldwide. Respondents needed to have a diagnosis of endometriosis and be aged between 18 and 55.
Results: A total of 1634 responses were received from 46 different countries. The average age of respondents was 30, with a mean diagnosis age of 25. Eight hundred forty-six respondents (51%) reported consuming cannabis
in the past 3 months, with 55% of these reporting use for symptom management only. One in five respondents (20%) reported having consumed cannabis previously, the most common reason for discontinuation (65%) was access difficulties during COVID. Those who had legal access were more likely to consume cannabis than those without ( p < 0.0001) and were more likely to disclose usage to health care professionals ( p < 0.0001). The most common reasons for consuming cannabis during COVID was increased stress/anxiety (59%) and lack of access to normal medical care (48%). Pre-pandemic, cannabis was mostly consumed at least once a day (61%) and in inhaled forms (51.6%). Consumption increased for most people (57%) during the pandemic. During the pandemic just under a quarter (23%) of respondents changed their mode of consumption, with a reduction in inhaled forms (39.5%) and an increase in consumption of edibles (40%) or oil (25.2%).
Conclusions: Cannabis consumption, especially for symptom relief, was relatively common among those with endometriosis, with some people starting their consumption of cannabis due to health care restrictions that occurred due to the COVID-19 pandemic. Difficulties accessing cannabis and unpleasant/unwanted side effects were the most common reasons for lack of current cannabis consumption in those who had previously consumed it. Cannabis consumption may form an important part of endometriosis management especially when access to routine medical care is restricted.
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FDA Issues Warning Letters to Companies Claiming Their CBD Products Can Treat COVID-19
April 1, 2022 – Cannabis Business Times News

https://www.cannabisbusinesstimes.com/article/fda-issues-warning-letters-to-companies-claiming-cbd-products-can-treat-covid-19/.
The federal agency is warning seven companies that they are falsely advertising their wares.

Several companies have been claiming that their CBD products can cure, treat, or prevent COVID-19, but the U.S. Food and Drug Administration (FDA) says they are wrong.
Seven companies—Cureganics, Heaven’s Organics LLC, Functional Remedies LLC, Greenway Herbal Products LLC, CBD Social, UPSY LLC and Nature’s Highway—received warning letters from the FDA in conjunction with the Federal Trade Commission (FTC) on March 28, according to a Miami Herald report.
The FDA and FTC are issuing warning letters to businesses that they say are “selling fraudulent products with claims to prevent, treat, mitigate, diagnose, or cure coronavirus disease 2019 (COVID-19),” according to the FDA’s website.
For example, in its letter to CBD Social, the FDA claims it “has observed that your website offers cannabidiol (CBD) products for sale in the United States and that these products are intended to mitigate, prevent, treat, diagnose, or cure COVID-19 in people. Based on our review, these products are unapproved new drugs sold in violation of section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. § 355(a). Furthermore, these products are misbranded drugs under section 502 of the FD&C Act, 21 U.S.C. § 352. The introduction or delivery for introduction of these products into interstate commerce is prohibited under sections 301(a) and (d) of the FD&C Act, 21 U.S.C. § 331(a) and (d).”
The warning letter says that CBD Social cited studies on its website to “misleadingly represent” its products “as safe and/or effective for the treatment or prevention of COVID-19,” including a 2021 National Institute of Health (NIH) study, a 2022 University of Chicago study, and a 2022 study from the American Chemical Society and American Society of Pharmacognosy. .

Fetal Exposure to Cannabis and Childhood Metabolic Outcomes: The Healthy Start Study

Brianna F. Moore, Katherine A. Sauder, Allison L. B. Shapiro, Tessa Crume, Gregory L. Kinney, and Dana Dabelea
The Journal of Clinical Endocrinology & Metabolism, 2022, XX, 1–8
DOI: 10.1210/clinem/dgac101

https://watermark.silverchair.com/dgac101.pdf?token=AQECAHi208BE 49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfK Ac485ysgAAAtswggLXBgkqhkiG9w0B BwagggLIMIICxAIBADCCAr0GCSqGSI b3DQEHATAeBglghkgBZQMEAS4wEQQM osS-Ac166NuJprghAgEQgIICjrXEbeMpY7 wlKwa-nHCx7tX1jjUSycrnvdHVl0rAYa2eLh vlbTQOk75T61fSct2bsZJNfpqXOtSY YoSXAgFJxUoiczKwCZP5wOrZ1KT4tJ tfWo7iIVH3mfvjoZ73AJeWZmbebdF1 E1R-ZSgLAIczIVVvh4ZoAi_dmFvXesoBji HOlVrDksVF--isiyrlcmoaoBxPpy22ky0wPMLw60WN Tjlx9SpWzjceAGD2_xtBfiG8_rLucA QwTix3Cu0PRno89dqNOhZ0Qf-lwgRDrrLkQ6czVaO8L_j21wXJtArsN WhGVvrP0DuCRim6ENgl6S63em1J2N6 akajz5cT2u1cP1mVXKFQ7sPMpwOHdu OcrX5tk8Ts7Hl25U-0MM1fgQiJzPvAdfIBgihoTiV2SSU7Q ZhNHjvqoTikVDZaBZ4ZfZ25F6rdqmH YDg4PSrOXEcu0fCpsiTrjQ4CeDPgtB GeYZDrYcgbVsPhmDEeG9egFBDmoWki ugAD2GrAssOGPi4ZRwdOj-8wSka6CrBm9EgdpkyUD0UGXFSkGxnN fG7yyksVsuCQBIMmYj09VtTP3LRuyC H2hzax6pmpwRSQozGvkjGJ9PIdkyEX 7Ulmv2pdfWYG9M_gI97_zWd-Git-QTAKbgeUpfsm2_1fkaCGI9e3-09AHnDC5BiWAkHQWEW0CwyTcjoCCan-_YmzD6DEc-c827D_JJ70ou5JpVoaaAKN1wI7VBSL knHZv2NWGOPTcqohB889nI0THZinRH jx7OlBFfhjaAO8__nNX1hc4-oipZYQz_DmVRE3KawjT_eqJOylikjY 2a-binjtJ5w0SQNY9YXhh49m_qTupmBcv Ghae-ow8AsO4dmRpZH2lJ0yX-pw

Objective: To assess the impact of fetal exposure to cannabis on adiposity and glucose-insulin traits in early life.
Research Design and Methods: We leveraged a subsample of 103 mother-child pairs from Healthy Start, an ethnically diverse Colorado-based cohort. Twelve cannabinoids/metabolites of cannabis (including Δ9-tetrahydrocannabinol and cannabidiol) were measured in maternal urine col­lected at ~27 weeks’ gestation. Fetal exposure to cannabis was dichotomized as exposed (any cannabinoid > limit of detection [LOD]) and not exposed (all cannabinoids < LOD). Fat mass and fat-free mass were measured via air displacement plethysmography at follow-up (mean age: 4.7 years). Glucose and insulin were obtained after an overnight fast. Generalized linear models estimated the associations between fetal ex­posure to cannabis with adiposity measures (fat mass [kg], fat-free mass [kg], adiposity [fat mass percentage], body mass index [BMI], and BMI z-scores) and metabolic measures (glucose [mg/dL], insulin [uIU/mL], and homeostatic model assessment of insulin resistance [HOMA-IR]).
Results: Approximately 15% of the women had detectable levels of any cannabinoid, indicating fetal exposure to cannabis. Exposed offspring had higher fat mass (1.0 kg; 95% CI, 0.3-1.7), fat-free mass (1.2 kg; 95% CI, 0.4-2.0), adiposity (2.6%; 95% CI, 0.1-5.2), and fasting glucose (5.6 mg/dL; 95% CI, 0.8-10.3) compared with nonexposed offspring. No associations were found with fasting insulin (in the fully adjusted model), HOMA-IR, BMI, or BMI z-scores.
Conclusions: We provide novel evidence to suggest an association between fetal exposure to cannabis with increased adiposity and fasting glucose in childhood, a finding that should be validated in other cohorts.
Key Words: DOHaD, fetal origins, pregnancy, cannabis, THC, CBD, child, obesity, glucose, insulin, metabolic syndrome .

Fine Particulate Matter Exposure From Secondhand Cannabis Bong Smoking

Patton Khuu Nguyen, S. Katharine Hammond
JAMA Network Open. 2022;5(3):e224744.
doi:10.1001/jamanetworkopen.2022.4744

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790510?xnpe_tifc=b.YdOfQNOfoX bDY8xIndxMpZhfEWVjQsVuU_O.VjOI olhkUstIYDhIbA4FP_hNl8bdhNtIHp bDPNxfb7bDHdb9puOIUNhkoJhkUL4k nD4dhN&utm_source=eNews&utm_ca mpaign=TCS%20Newsletter%20Week %2014%202022&utm_medium=email
Introduction

Secondhand cannabis smoke (SHCS) is a novel exposure source uncharacterized in homes but containing known health risk factors.1 Although 27%of young adults believe SHCS exposure is safe,2 cannabis smoke has several hundred toxic chemicals, carcinogens, and fine particulate matter (PM2.5), many at higher concentrations than tobacco smoke.1 Decades of secondhand tobacco smoke (SHTS) research demonstrate causal links to cancer, respiratory and cardiovascular diseases, preterm birth, and decreased immune function.3 These concerns have not translated to cannabis bong smoking, a popular consumption method in social settings among young adults, wherein smoke is drawn through water. However, like SHTS, 1 minute of SHCS caused significant endothelial dysfunction in rats.4 This cohort study measured PM2.5 levels from social bong smoking; it is the first, to our knowledge, to quantify SHCS levels from social cannabis smoking in the home.
Methods

Levels of PM2.5 were measured before, during, and after 8 cannabis social-smoking sessions in one 20-m2 household living room (eMethods in the Supplement). An aerosol monitor (SidePak AM510; TSI Inc) measured PM2.5 concentrations where a nonsmoker might sit. The University of California, Berkeley, Office for the Protection of Human Subjects deemed this study not human participants research and waived review. This study followed the STROBE reporting guideline. The Wilcoxon rank sum 2-sided test assessed statistical differences between PM2.5 concentrations before and during smoking. Analysis was performed using RStudio, version 1.4 (RStudio). Two-sided P < .05 indicated statistical significance.
Results

Home cannabis bong smoking significantly increased PM2.5 from background levels (conditions existing before the smoking began) in all sessions by 100-fold to 1000-fold for 6 of 8 sessions; the other 2 sessions had high background and significantly increased PM2.5 more than 20-fold (P < .001 for all 8 sessions). During the first 10 minutes of smoking, mean (SD) PM2.5 concentrations increased to 410 (220) μg/m3, after 15 minutes to 570 (290) μg/m3, after 30 minutes to 1000 (320) μg/m3, and went as high as 2500 μg/m3 in 1 session (Figure). The concentration during smoking increased to a mean (SD) of 1300 (280) μg/m3 (Table). During 2-hour smoking sessions, mean (SD) 5-minute peak PM2.5 concentration was 1700 (460) μg/m3 and remained half that 90 minutes after smoking ceased. Each half hour after smoking ceased, mean concentration declined to 78%of peak value, then 60%, then 40%, and, after 110 minutes, 31%. In the 1 session monitored for 12 hours after smoking stopped, PM2.5 remained elevated at 50 μg/m3, more than 10 times the background concentration. Cannabis bong smoking in the home generated 4 times greater PM2.5 concentrations than cigarette or tobacco hookah (waterpipe) smoking (Table).
Discussion

The PM2.5 concentrations generated in a home during social cannabis bong smoking to which a nonsmoking resident might be exposed were greatly increased compared with background levels, and PM2.5 decayed only gradually after smoking ceased. After 15 minutes of smoking, mean PM2.5 (570 μg/m3) (Figure)was more than twice the US Environmental Protection Agency (EPA) hazardous air quality threshold (>250 μg/m3). If one assumes the exposure concentrations were at the mean levels observed, a single home smoking session with no other exposures would generate an estimated mean daily concentration (200 μg/m3) that greatly exceeds the average in cigarette smoking homes (44 μg/m3), nonsmoking homes (15 μg/m3), and the US EPA daily standard (35 μg/m3).3 A strength of this study is that measurements were made during actual social bong smoking sessions without artificial constraints. Limitations include that cannabis smoking was not directly
observed. .

Glucocorticoids shift arachidonic acid metabolism toward endocannabinoid synthesis: A non-genomic anti-inflammatory switch

Renato Malcher-Lopes, Alier Franco, Jeffrey G. Tasker
European Journal of Pharmacology 583 (2008) 322–339
doi:10.1016/j.ejphar.2007.12.033
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367369/
Glucocorticoids are capable of exerting both genomic and non-genomic actions in target cells of multiple tissues, including the brain, which trigger an array of electrophysiological, metabolic, secretory and inflammatory regulatory responses. Here, we have attempted to show how glucocorticoids may generate a rapid anti-inflammatory response by promoting arachidonic acid-containing endocannabinoids biosynthesis. According to our hypothesized model, non-genomic action of glucocorticoids results in the global shift of membrane lipid metabolism, subverting metabolic pathways toward the synthesis of the anti-inflammatory endocannabinoids, anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG), and away from arachidonic acid production. Post-transcriptional inhibition of cyclooxygenase-2 (COX2) synthesis by glucocorticoids assists this mechanism by suppressing the synthesis of pro-inflammatory prostaglandins as well as endocannabinoid-derived prostanoids. In the central nervous system (CNS) this may represent a major neuroprotective system, which may cross-talk with leptin signaling in the hypothalamus allowing for the coordination between energy homeostasis and the inflammatory response. .

Quality Standards in State Programs Permitting Cannabis for Medical Uses
Schuyler A. Pruyn, Qiang Wang, Charles G. Wu, and Cassandra L. Taylor
Cannabis and Cannabinoid Research Volume X, Number X, 2022

DOI: 10.1089/can.2021.0164
Currently in the United States, there exists a patchwork of state-level laws and regulations surrounding cannabis use. Although cannabis (excluding hemp under the Agricultural Improvement Act of 2018, Public Law 115-334) is illegal at the federal level and is not FDA (U.S. Food and Drug Administration) approved for any indication, many states allow patients with qualifying conditions to register for their medical cannabis program(MCP). To better understand the quality of cannabis found in these programs, we collected laws, regulations, and guidance documents available on public state-run websites and compared them with current good manufacturing practices (CGMPs) applicable to finished drug products. CGMPs for human drugs contain minimum requirements for the methods, facilities, and controls used in manufacturing, processing, and packaging of a drug product to assure it is safe for use. Such a comparison will aid the development of consistent quality standards that could, in turn, improve the quality of a wide range of cannabis medical products in development that may be sold in the United States. States may likewise choose to have the cannabis and cannabis-derived products that fall within their MCP to follow quality-focused guidelines, such as those listed in CGMPs, to ensure the quality of these products and promote public health.
This study further solidifies the need for standardized testing protocols and methodologies to keep consumers safe.
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Role of acylethanolamides in the gastrointestinal tract with special reference to food intake and energy balance.
Francesca Borrelli, Angelo A. Izzo
Best Practice & Research Clinical Endocrinology & Metabolism 23 (2009) 33–49
Doi: 10.1016/j.beem.2008.10.003
https://www.researchgate.net/publica...l_reference_to _food_intake_and_energy_balanc e

Acylethanolamides (AEs) are a group of lipids occurring in both plants and animals. The best-studied AEs are the endocannabinoid anandamide (AEA), the anti-inflammatory compound palmitoylethanolamide (PEA), and the potent anorexigenic molecule oleoylethanolamide (OEA). AEs are biosynthesized in the gastrointestinal tract, and their levels may change in response to noxious stimuli, food deprivation or diet-induced obesity. The
biological actions of AEs within the gut are not limited to the modulation of food intake and energy balance. For example, AEs exert potential beneficial effects in the regulation of intestinal motility, secretion, inflammation and cellular proliferation. Molecular targets of AEs, which have been identified in the gastrointestinal tract, include cannabinoid CB1 and CB2 receptors
(activated by AEA), transient receptor potential vanilloid type 1 (TRPV1, activated by AEA and OEA), the nuclear receptor peroxisome proliferators-activated receptor-a (PPAR-a, activated by OEA and, to a less extent, by PEA), and the orphan G-coupled receptors GPR119 (activated by OEA) and GPR55 (activated by PEA and, with lower potency, by AEA and OEA). Modulation of AE levels in the gut may provide new pharmacological strategies not only for the treatment of feeding disorders but also for the prevention or cure of widespread intestinal diseases such as inflammatory bowel disease and colon cancer. .

Role of the Endogenous Cannabinoid System in Nicotine Addiction: Novel Insights
Islam Hany Gamaleddin, Jose M. Trigo, Aliou B. Gurye, Alexander Zvonok, Alexandros Makriyannis, Steven R. Goldberg and Bernard Le Foll
DOI: 10.3389/fpsyt.2015.00041
https://www.ncbi.nlm.nih.gov/pmc/art...t-06-00041.pdf
Several lines of evidence have shown that the endogenous cannabinoids are implicated in several neuropsychiatric diseases. Notably, preclinical and human clinical studies have shown a pivotal role of the cannabinoid system in nicotine addiction. The CB1 receptor inverse agonist/antagonist rimonabant (also known as SR141716) was effective to decrease nicotine-taking and nicotine-seeking in rodents, as well as the elevation of dopamine induced by nicotine in brain reward area. Rimonabant has been shown to improve the ability of smokers to quit smoking in randomized clinical trials. However, rimonabant was removed from the market due to increased risk of psychiatric side-effects observed in humans. Recently, other components of the endogenous cannabinoid system have been explored. Here, we present the recent advances on the understanding of the role of the different components of the cannabinoid system on nicotine’s effects. Those recent findings suggest possible alternative ways of modulating the cannabinoid system that could have implication for nicotine dependence treatment. . .

The efficacy and safety of cannabidivarin treatment on epilepsy in girls with Rett syndrome: A phase 1 clinical trial
Ellen N Hurley, Carolyn J Ellaway, Alexandra M Johnson, Linda Truong, Rebecca Gordon, Peter Galettis, Jennifer H Martin, John A Lawson
Epilesia April 2022
doi: 10.1111/EPI.17247
https://onlinelibrary.wiley.com/doi/10.1111/epi.17247
Objective: Rett Syndrome (RTT), commonly caused by methyl-CpG-binding protein 2 (MECP2) pathogenic variants, has many co-morbidities. 50-90% of children with RTT have epilepsy which is often drug resistant. Cannabidivarin (CBDV), a non-hallucinogenic phytocannabinoid has shown benefit in MECP2 animal models. This Phase I trial assessed the safety and tolerability of CBDV in female children with RTT and drug resistant epilepsy, as well as the effect on mean monthly seizure frequency (MMSF), the electroencephalogram (EEG), and non-epilepsy comorbid symptoms.
Methods: Five female children with drug resistant epilepsy and a pathogenic MECP2 variant were enrolled. Baseline clinical and laboratory assessments, including monthly seizure frequency, were recorded. CBDV oral solution (50mg/mL) was prescribed and titrated to 10mg/kg/day. Data collected over 15 months included pharmacokinetics, seizure type and frequency, adverse events, EEG, and responses to Rett syndrome behaviour questionnaire (RSBQ) and Rett syndrome symptom severity index, and was compared to baseline data.

Results: All five children reached the maximum CBDV dose of 10mg/kg/day and had a reduction in MMSF (median 79% reduction). Three children had MMSF reduction >75%. This corresponded to an overall reduction in seizure frequency from 32 to 7.2 seizures per month. 91% of adverse events were mild or moderate and none required drug withdrawal. 62% were judged unrelated to CBDV. 31% of adverse events were identified as possibly related, of which nearly all were mild, and the remainder were later assessed as RTT symptoms. Hypersomnolence and drooling were identified as related to CBDV. No serious adverse events reported were related to CBDV. No significant change was noted in EEG or non-epilepsy related symptoms of RTT.
Significance: 10mg/kg/day of CBDV is safe and well tolerated in a paediatric Rett syndrome cohort and suggests improved seizure control in children with MECP2-related Rett syndrome.

The Endocannabinoid System and Anxiety
S.F.Lisboa,F.V. Gomes, A.L.B. Terzian, D.C. Aguiar, F.A. Moreira, L.B.M. Resstel, F.S. Guimarães
Vitamins and Hormones Volume 103, 2017, Pages 193-279
DOI: 10.1016/bs.vh.2016.09.006

The medical properties of Cannabis sativa is known for centuries. Since the discovery and characterization of the endogenous cannabinoid system, several studies have evaluated how cannabinoid compounds and, particularly, how the modulation of the endocannabinoid (eCB) system influences a wide range of functions, from metabolic to mental disorders. Cannabinoids and eCB system often exert opposite effects on several functions, such as anxiety. Although the mechanisms are not completely understood, evidence points to different factors influencing those effects. In this chapter, the recent advances in research about the relationship between eCB system and anxiety disorders in humans, as well as in animal models, will be discussed. The recent data addressing modulation of the eCBs in specific brain areas, such as the medial prefrontal cortex, amygdaloid complex, bed nucleus of stria terminalis, hippocampus, and dorsal periaqueductal gray, will be summarized.
Finally, data from animal models addressing the mechanisms through which the eCB system modulates anxiety-related behavior dependent on stressful situations, such as the involvement of different receptors, distinct eCBs, modulation of neurotransmitters release, HPA axis and immune system activation, and plastic mechanisms, will also be discussed. .

The in vitro efect of delta-9-tetrahydrocannabinol and cannabidiol on whole blood viscosity, elasticity and membrane integrity

Tameika R. James, Andrea A. Richards, Dwight A. Lowe, Walton A. Reid, Charah T. Watson and Dagogo J. Pepple
Journal of Cannabis Research (2022) 4:15
DOI: 10.1186/s42238-022-00126-z
Background: The main biological activities of cannabis are due to the presence of several compounds known as cannabinoids. Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are two of the main cannabinoids. Studies have shown that the efects of THC can be modulated by CBD. Objective: This study aims to look at the efect of diferent concentrations of THC and CBD separately and in combination, on blood viscosity, elasticity and membrane integrity. Methods: Blood samples were collected from twenty-four healthy adult non-smokers. Blood viscosity and elasticity were determined using the Vilastic Scientifc Bioprofler for diferent concentrations (0, 2.5, 25, 50 and 100ng/ml) of CBD and THC respectively, as well as in extracts with combinations of CBD and THC in 4:1 and 1:1 ratios respectively. Repeated measures analysis of variance (ANOVA) was used to determine the diference between the means of the groups. Results: Blood viscosity increased signifcantly with increasing concentrations of both THC and CBD from 25ng/ ml up to 100ng/ml ranging from 6.45±0.36mPa·s to 11.60±1.12mPa·s for THC and ranging from 5.46±0.24mPa·s to 9.91±1.10mPa·s for CBD respectively, being more pronounced in the extracts at 21.33±2.17mPa·s for the 4THC:1CBD extract and 21.76±1.88mPa·s for the 1THC:1CBD extract. There was no signifcant increase in elasticity for THC and CBD separately. However, a signifcant increase in elasticity was observed in the extracts. THC and CBD afected red cell morphology resulting in complete disintegration at the highest concentrations. Conclusions: THC and CBD increased red blood cell viscosity and elasticity separately and in combination. They also adversely afected membrane integrity.
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The Potential of Salivary Lipid-Based Cannabis-Responsive Biomarkers to Evaluate Medical Cannabis Treatment in Children with Autism Spectrum Disorder

Michael Siani-Rose, Robert McKee, Stephany Cox, Bonni Goldstein,
Donald Abrams, Myiesha Taylor, and Itzhak Kurek Cannabis and Cannabinoid Research (march 2022)
https://doi.org/10.1089/can.2021.0224
https://www.liebertpub.com/doi/10.10...m_medium=email
Introduction: Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental conditions affecting social communication and social interaction. Medical cannabis (MC) treatment shows promising results as an approach to reduce behavioral difficulties, as determined mainly by subjective observations. We have recently shown the potential of cannabis-responsive biomarkers detected in saliva of children with ASD to objectively quantify the impact of successful MC treatment using a metabolomics approach. Since the pathology of ASD is associated with abnormal lipid metabolism, we used lipidomics on the same samples to (1) expand the repertoire of cannabis-responsive biomarkers and (2) provide preliminary insight into the role of MC on lipid metabolism.
Materials and Methods: Saliva samples collected from children with ASD (n=15) treated with MC (both before and at the time of maximal impact of treatment) and an age-matched group of typically developing (TD) children (n=9) were subjected to untargeted lipidomics. The study was observational. Each child from the ASD group was receiving a unique individualized MC treatment regimen using off-the-shelf products as permitted by California law under physician supervision for at least 1 year. Doses of tetrahydrocannabinol (THC) ranged from 0.05 to 50mg and cannabidiol (CBD) from 7.5 to 200mg per treatment. The ASD group was evaluated for signs of improvement using parental brief Likert scale surveys.
Results: Twenty-two potential lipid-based cannabis-responsive biomarkers exhibiting a shift toward the TD physiological levels in children with ASD after MC treatment were identified. Members from all five lipid subclasses known to be present in saliva were characterized. Preliminary lipid association network analysis suggests involvement of two subnetworks previously linked to (1) inflammation and/or redox regulation and (2) oxidative stress. The significant changes in sphingomyelin in this study and in N-acetyl-aspartate (NAA) previously detected in the metabolomics analysis of the same saliva samples may indicate a role of MC in neuron function.
Conclusions: Our findings suggest that lipid metabolites in saliva can potentially serve as cannabis-responsive biomarkers and objectively quantify the impact of MC treatment, and indicate a possible mechanism of action for MC. This preliminary study requires further investigation with a larger population and appropriate clinical trial monitoring. Link with paper
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IC Terpenes 1 .

Vapor Phase Terpenes Mitigate Oxidative Degradation of Cannabis sativa Inflorescence Cannabinoid Content in an Accelerated Stability Study

Justin Bueno, Solmaz Alborzi, and Eric A. Greenbaum Cannabis and Cannabinoid Research Volume X, Number X, 2022
DOI: 10.1089/can.2021.0207
Introduction: As Cannabis sativa L. (Cannabaceae) ages, inflorescence phytochemicals are susceptible to oxidative degradation. Reduction of D9-tetrahydrocannabinol (D9-THC) content has the potential to impact the reliability and accuracy of dosing. Advances that improve cannabinoid stability during storage would have an important impact in medical cannabis markets. Reported here is the use of C. sativa terpenes with antioxidant properties that improve inflorescence cannabinoid stability.
Materials and Methods: Killer Kush inflorescence samples were stored in a temperature-controlled environment, in opaque jars. To accelerate the rate of oxidate degradation, samples were stored with the oxidizing agent hydrogen peroxide. Vapor phase terpenes were added to inflorescence packaging. Two terpene blends and three different dosage amounts were evaluated. Inflorescence stability samples were prepared in triplicate for each sample type. Cannabinoid content was quantitatively assessed after 24, 81, and 127 days of storage using high-performance liquid chromatography. Terpene content was assessed using headspace gas chromatography mass spectrometry. Results from inflorescence stored with and without external terpenes were compared by analysis of variance (ANOVA) data processing.
Results: After 127 days of storage, inflorescence in the accelerated study experienced a loss of 18.0% and 34.3% total D9-THC content for samples stored with and without external terpenes, respectively. The differences in cannabinoid content were found to be statistically significant at all time points using ANOVA processing. In the non accelerated study, only one of the six sample types investigated had a statistically significant greater total D9-THC content than control at all time points. Nevertheless, a dose-dependent relationship between the amount of external terpenes added to inflorescence and the preservation of total D9-THC content was observed.
Discussion: In the accelerated study, exogenous terpenes reduced the degradation of inflorescence cannabinoid content by 47.4%. This represents the first reported addition of terpene antioxidants to inflorescence packaging for cannabinoid preservation. Of note, the antioxidants used in this system can be obtained from C. sativa. This is advantageous from a toxicological perspective as inhaling synthetic antioxidants presents unknown and unpredictable risks. When fully developed, the novel system has applications for inflorescence packaged for individual sale, as well as long-term storage of bulk biomass.
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Last edited:

Rico Swazi

Active member
You mean here on ICMag? Once you're in the right section use your browser's built in search (keyboard shortcut Ctrl-F on most browsers or something along the lines of "Find" in the menu).

Thanks for the reply, wanted to use the forum search function, not the browser find in page which is a useful tool but clunky. The * (asterisk) skewed my search results using find whereas a search of same phrase gave up the correct link with Xenforo (which disregards the * (asterisk) or other common words). Best part showing results in links on a new page. See thumbs

Problem solved and couldn't be happier to be able to search this valuable resource properly. Many many thanks to those that make this possible.

Sam and everyone..., looking to find a free PDF for this one-

A rapid method for sex identification in Cannabis sativa using high resolution melt analysis

We report the identification of two single nucleotide polymorphisms in Cannabis sativa L. that are associated with female and male plant sex phenotypes and are located on the top arm of the X chromosome. High resolution melt analysis was used to develop and validate a novel, rapid method for sex identification in medical and (or) recreational cannabis as well as in hemp. This method can distinguish between dioecious male (XY) and dioecious female (XX) cannabis plants with 100% accuracy and can also be used to differentiate between male and female Humulus lupulus L. (hop) plants.

 

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Sam_Skunkman

"RESIN BREEDER"
Moderator
Veteran
I can not add new links because it says the files are to big, no problem before, but I can not add to the IC BIB Threads or even like I did in post #284 & 288 WTF?
I need help I asked Gypsy and he said he would find a way, but so far nada. I will have many to post when I can post new additions into the old IC BIB, until then I can do nothing.
 

StevenHXF

Well-known member
Administrator
I can not add new links because it says the files are to big, no problem before, but I can not add to the IC BIB Threads or even like I did in post #284 & 288 WTF?
I need help I asked Gypsy and he said he would find a way, but so far nada. I will have many to post when I can post new additions into the old IC BIB, until then I can do nothing.
Hi Sam,

I’ve tried pming you about this twice and didn’t get a response.

Are you trying to post a new post in this thread or edit one of the existing posts in this thread? I need to know exactly what the issue is before I know what settings need to be changed. Get back to me and we’ll sort it out.

Steven
 

Sam_Skunkman

"RESIN BREEDER"
Moderator
Veteran
Hi Sam,

I’ve tried pming you about this twice and didn’t get a response.

Are you trying to post a new post in this thread or edit one of the existing posts in this thread? I need to know exactly what the issue is before I know what settings need to be changed. Get back to me and we’ll sort it out.

Steven
I am trying to add new links to the existing threads I get a notice the post is to big to add to. I did not see your PM but the new format makes using it difficult, or maybe I am just an old codger?
 

StevenHXF

Well-known member
Administrator
I am trying to add new links to the existing threads I get a notice the post is to big to add to. I did not see your PM but the new format makes using it difficult, or maybe I am just an old codger?
Maybe it’s a bit of both? 😂

So I think the issue is going to be down to character limits. Give me a few minutes to see if it can be increased.
 

Sam_Skunkman

"RESIN BREEDER"
Moderator
Veteran
I tried both neither workd the single post with all the new ones (40) is 9742 words so I can not post it in a single new post I also can not add anything to the old posts because the old posts are all bigger then that, I am down to posting just a few new links at a time in a new post like I did in Post #302, that did work but is no use as I want to edit & add them to my old posts, but I will also post all the new links together like I did for #284 & #288 so folks can see the new papers and find them in the BIB if interested.
 

Sam_Skunkman

"RESIN BREEDER"
Moderator
Veteran
The word count of the new 40 articles is 9742 that is the 40 new articles for the BIB, like in Post #302, that is one of the 40 new articles I want to post alphabetized in with the others, by Subjects.
 
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