41 New articles added to IC BIB WWW
April 21
2 in IC Cannabinoids
6 in IC Cannabis Analysis
5 in IC Cannabis Botany
4 in IC Legal
9 in IC Medical Cannabis/Endocannabinoids Pt 1 A-D
15 in IC Medical Cannabis/Endocannabinoids Pt 2 E-Z
IC Cannabinoids 2
Associations between cannabinoids and growth stages of twelve industrial hemp cultivars grown outdoors in Atlantic Canada
Nada Hammami, Jean-Pierre Privé, David L Joly, Gaétan Moreau Industrial Crops and Products 172(29):113997 Nov 2021 DOI: 10.1016/j.indcrop.2021.113997
https://www.researchgate.net/public...p_cultivars_grown_outdoors_in_Atlantic_Canada
Industrial hemp is increasingly grown and harvested for its cannabinoids of pharmaceutical interest. These compounds are generally obtained from plants harvested at maturity but not all cannabinoids are present or abundant during the last stage of hemp development. This study examined intraspecific cannabinoid variability during ontogenic development of hemp to identify growth stages and cultivars that optimize production of specific compounds. The cannabinoid content of twelve commercial industrial hemp (Cannabis sativa L. subsp. sativa) cultivars at three growth stages (i.e., flowering, grain filling and maturity) was determined by high performance liquid chromatography in an experimental field in Cocagne, New Brunswick, Canada. Most cannabinoids in acidic or neutral form were more abundant at maturity. However, cannabigerolic acid, a precursor to all acidic and neutral forms of cannabinoids mentioned in our study, was more abundant during the grain-filling stage. In contrast, cannabichromene was associated with the flowering stage and found in greater abundances in grain cultivars than in dual-purpose cultivars. The cultivar Katani exhibited higher concentrations of most cannabinoids while the cultivars Ferimon, Altair and Anka exhibited higher concentrations of cannabinoid acidic precursors. The current study could help optimize the targeted production of cannabinoids at specific growth stages and to identify the chemical phenotype of different hemp cultivars. .
Cannabinoid modulation of mother-infant interaction: is it just about milk?
Antonia Manduca, Patrizia Campolongo and Viviana Trezza
Rev. Neurosci. 2012; 23(5-6): 707–722
DOI 10.1515/revneuro-2012-0074
Mother-infant interactions are essential for proper neurobehavioral development of the offspring, and disruptions in those relationships may result in neuroendocrine, neurochemical and behavioral alterations at adulthood. The neural circuitries involved in mother-infant interactions have not been completely elucidated yet. The brain endocannabinoid system plays an essential role in prenatal and postnatal neurobehavioral development. Here, we will summarize and discuss the available findings about the role of endocannabinoids in three key aspects of mother-infant interactions in rodents: suckling, maternal behavior and separationinduced ultrasonic vocalizations (USVs). The studies reviewed here show that endocannabinoids are not only involved in suckling initiation and, therefore, in the feeding and growth of the offspring, but also regulate the emotional reactivity of rodent pups, as measured by the rate of isolation-induced USVs. Conversely, less information is available about endocannabinoid modulation of maternal behavior, and therefore more research in this direction is warranted. Indeed, since Cannabis sativa preparations are widely used by young people, including pregnant and lactating women, it is important to understand whether developmental exposure to cannabinoids interferes with mother-infant bond formation, potentially leading to neurodevelopmental alterations and increased vulnerability to psychopathology later in life.
New hemp (Cannabis sativa L.) strains developed by crossbreeding selected varieties represent a novel research topic worthy of attention and investigation. This study focused on the phytochemical characterization of nine hemp commercial cultivars. Hydrodistillation was performed in order to collect the essential oils (EO), and also the residual water and deterpenated biomass. The volatile fraction was analyzed by GC-FID, GC-MS, and SPME-GC-MS, revealing three main chemotypes. The polyphenolic profile was studied in the residual water and deterpenated biomass by spectrophotometric assays, and HPLC-DAD-MSn and 1H-NMR analyses. The latter were employed for quali–quantitative determination of cannabinoids in the deterpenated material in comparison with the one not subjected to hydrodistillation. In addition, the glandular and non-glandular indumentum of the nine commercial varieties was studied by means of light microscopy and scanning electron microscopy in the attempt to find a possible correlation with the phytochemical and morphological traits. The EO and residual water were found to be rich in monoterpene and sesquiterpene hydrocarbons, and flavonol glycosides, respectively, while the deterpenated material was found to be a source of neutral cannabinoids. The micromorphological survey allowed us to partly associate the phytochemistry of these varieties with the hair morphotypes. This research sheds light on the valorization of different products from the hydrodistillation of hemp varieties, namely, essential oil, residual water, and deterpenated biomass, which proved to be worthy of exploitation in industrial and health applications. .
Cannabinoid Quantitation via Rugged and Adaptable HPLC/UHPLC Method Development
The Analytical Scientist & phenomenex 04/23/2020 WebVideo
https://thecannabisscientist.com/webinar/cannabinoid-quantitation-via-rugged-and-adaptable-hplc/uhplc-method-development?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
https://view6.workcast.net/register?cpak=8256969521182128
https://view6.workcast.net/registerthanks?regtracker=ftxfw1yaOQjOZY6KSLd1YcuAb4nsm56VJU18/grmNy1DZOW1gogLZIagxVWSojlk
https://view6.workcast.net/AuditoriumAuthenticator.aspx?cpak=8256969521182128&pak=7298980096326304
Potency testing demands in the cannabis industry have exploded and are continuing to expand in product formulations, applications, and plant cultivations. Of the hundreds of known cannabinoid molecules, six have been of primary interest to quantitate (THC, THC-A, CBD, CBD-A, CBG, and CBG-A). With various regulations, such as the Farm Bill, distinguishing between Marijuana and Hemp through levels of intoxicating cannabinoids, specific and accurate quantitation of these cannabinoids is ever more critical and even more challenging with a rising number and level of minor cannabinoids potentially present from chemical reactions or novel cultivars. Along with the sheer number of potentially interfering cannabinoids, their chromatographic profiles are a challenge to maintain as their retention profiles can have significant shifts from minute changes in common chromatographic conditions. Here we’ll cover the key underlying chromatographic factors to ensure robust and rugged potency method development that can be adapted readily to accommodate the dynamic landscape.
Learning Objectives
Mobile phase factors applied to method accuracy and ruggedness.
Instrument and method transfer considerations in robustness.
Critical cannabinoids resolved chromatographically.
Learning Objectives of Webinar
Learning Objectives:
Margot Lespade | 04/20/2022
Structure elucidation of the tetrahydrocannabinol complex with randomly methylated -cyclodextrin
Arno Hazekamp, Rob Verpoorte
european journal of pharmaceutical sciences 29 (2006) 340–347
Doi: 10.1016/j.ejps.2006.07.001
The low aqueous solubility of the bioactive cannabinoid tetrahydrocannabinol (THC) is a serious obstacle for the development of more efficient administration forms. In this study the aqueous solubility of THC was tested in the presence of -, - and -CD, and randomly methylated -CD (RAMEB). It was found that only RAMEB was able to increase the aqueous solubility of THC to a significant level. A THC concentration of about 14mg/ml was reached by using a 24% (187mM) RAMEB solution, which means an increase in solubility of four orders of magnitude. The resulting THC/RAMEB complex was investigated through phase-solubility analysis, complemented by 1H NMR, NOESY- and UV-studies in order to obtain details on the stoichiometry, geometry and thermodynamics of the complexation. The binding ratio of THC to CD was found to be 2:1, with the second THC molecule bound by non-inclusion interactions. Based on the obtained results a model for the complex structure is presented. Stability of the complex under laboratory room conditions was tested up to 8 weeks. Results show that complexation with RAMEB seems to be promising for the development of waterbased THC formulations
IC Cannabis Botany 5 .
Associations between cannabinoids and growth stages of twelve industrial hemp cultivars grown outdoors in Atlantic Canada
Nada Hammami, Jean-Pierre Privé, David L Joly, Gaétan Moreau Industrial Crops and Products 172(29):113997 Nov 2021 DOI: 10.1016/j.indcrop.2021.113997
https://www.researchgate.net/public...p_cultivars_grown_outdoors_in_Atlantic_Canada
The cannabis industry hit a possible milestone in March when Bright Green Corp., a Florida company with “conditional” approval from the U.S. Drug Enforcement Administration to grow marijuana for research purposes, applied to list on the Nasdaq stock exchange.
If successful, Bright Green would become the first U.S. plant-touching company to list on a major U.S. stock exchange.
But the move also highlights the lofty – some say unrealistic – financial ambitions of such companies.
And it raises the question of whether a business model based on DEA approval is realistic from a financial standpoint.
The five entities registered with the DEA as “Bulk Manufacturer Marihuana Growers” are allowed to grow and sell marijuana flower and extract to researchers registered with the federal agency.
Those researchers can be at universities, pharmaceutical companies and other entities.
The University of Mississippi received the first DEA cultivation registration in 1968, while four more entities received registrations in 2021.
Three of the other four entities that have secured DEA approval are private companies, while the Scottsdale Research Institute in Cave Creek, Arizona, is a nonproft focused on determining “the general medical safety and efficacy of cannabis and cannabis products.”
Other entities, such as Fort Lauderdale-based Bright Green, are vying for additional registrations, although it’s not clear if or when the DEA will issue any more.
In addition to making money through the cultivation of marijuana for scientific research, at last three of the DEA-approved companies hope to further capitalize on cannabis-based drug development.
They are:
Biopharmaceutical Research Co., in Castroville, California.
Groff North America, in Red Lion, Pennsylvania.
Royal Emerald Pharmaceuticals, in Desert Hot Springs, California.
How can such drug development be a money winner?
The answer? By partnering with pharmaceutical companies and multistate operators to develop drugs approved by the U.S. Food and Drug Administration that could be sold by prescription or even over the counter.
Each company attained DEA bulk cannabis manufacturing registration in 2021.
“Conceptually, the opportunity is phenomenal. If you total up all the pharmaceutical sales for the indications that cannabis can address, like sleep pain, nausea, etc., it’s a $330 billion-a-year market. There’s lots and lots of activity to be had in this pharmaceutical facilitator area,” said Joe Grzyb, CEO of Groff North America.
But he added: “You have to be patient, because it takes several years to get through the FDA process.”
Doubts over DEA-based business model
Sue Sisley, head of the Scottsdale Research Institute – which is among the five DEA cannabis cultivation registrants – said business models based on the DEA registrations are bound to fail.
“The entities who are trying to build a business model around these few research registrations won’t be successful. The demand for research cannabis is minimal,” Sisley said.
“This is not a lucrative business model and never will be. It takes over 10 years to develop drugs that get FDA approval – and is massively more complicated when it comes to agricultural products that have complex chemical composition with tons of different bioactive molecules.”
The University of Mississippi received the first DEA permit to grow cannabis for research in 1968.
Effect of Timing of Ethephon Treatment on the Formation of Female Flowers and Seeds from Male Plant of Hemp (Cannabis sativa L.
Youn-Ho Moon, Yoon Jeong Lee, Sung Cheol Koo, Mok Hur, Yun Chan Huh, Jae-Ki Chang and Woo Tae Park
Korean J. Plant Res. 33(6):682-688(2020)
DOI: 10.7732/kjpr.2020.33.6.682
http://203.250.217.22/article/JAKO202034965719736.pdf
Hemp (Cannabis sativa L.) is a dioecious plant, although monoecious plants are bred in some cultivars for fiber or seed production. Recently, hemp has received attention for medicinal use with some cannabinoids, including cannabidiol. Self-fertilization for breeding inbred lines is difficult because of dioeciousness and anemophily in hemp. This experiment was conducted to develop a self-fertilization method by forming female flowers and seeds from male plants of dioecious hemp. To induce the formation of female flowers on male plants, 500 ㎎ L-1 of ethephon was sprayed on plants at soon, seven and fourteen days after primordia formation. The plant ratio of female flowers formation and the number of harvested seeds were increased by ethephon treatment. Female flowers of male plants have 5 stigmas in contrast to the dual stigma of female 1plants. Male plant seeds were lighter and smaller than those from female plants. Although the germination rate was lower than that of normal seeds from female plants, the seeds from male plants germinated to grow seedlings. Thus, we suggest that hemp plants should be treated with ethephon at soon after primordia formation to induce the formation of more female flowers on the male plants. .
INFLUENCE OF STORAGE AND MIXING FACTORS ON THE BIOLOGICAL ACTIVITY OF SILVER THIOSULFATE
ARTHUR C. CAMERON, ROYAL D. HEINS and HAROLD N. FONDA
DOI: 10.1016/0304-4238(85)90009-3
Scientia Horticulturae, 26 (1985) 167--174
Silver thiosulfate (STS) complex stability and degradation during formulation and storage were monitored indirectly by determining the effectiveness of treatment solutions in retarding flower petal abscission in geraniums (Pelargonium hortorum Baily). Freshly prepared solutions composed of Ag+:S2032- ratios from1:1 to 1:16 at constant silver concentration were all equally effective. There were no differences in effectiveness when a Ag+:S2032- solution of ratio 1:4 was formulated at 5, 25 or 50°C, when prepared at pH 4.01, 7.0 or 10.0, or when prepared in the presence of 10 mM KC1, Na2CO3, Ca(NO3) 2 or MgSO~. The ability of solutions to retard abscission was reduced when Ag + was substantially in excess of $2032-. Rapid mixing of AgNO3 and Na2S~O3 solutions yielded effectiw~ solutions, independent of mixing order. Complete loss of activity was observed when solutions were stored in contact with either tin or galvanized metal for 5 days, whereas there was no loss in activity after 3 months' storage in plastic or glass at 2°C. These results indicate that currently recommended formulation procedures are unnecessarily stringent, and that long-term cold storage of prepared STS solutions is feasible.
Root-TRAPR: a modular plant growth device to visualize root development and monitor growth parameters, as applied to an elicitor response of Cannabis sativa
Pipob Suwanchaikasem, Alexander Idnurm, Jamie Selby‐Pham, Robert Walker and Berin A. Boughton
Suwanchaikasem et al. Plant Methods (2022) 18:46
DOI: 10.1186/s13007-022-00875-1
https://www.researchgate.net/public...icitor_response_of_Cannabis_sativa/references
Background: Plant growth devices, for example, rhizoponics, rhizoboxes, and ecosystem fabrication (EcoFAB), have been developed to facilitate studies of plant root morphology and plant‐microbe interactions in controlled labora‐ tory settings. However, several of these designs are suitable only for studying small model plants such as Arabidopsis thaliana and Brachypodium distachyon and therefore require modification to be extended to larger plant species like crop plants. In addition, specific tools and technical skills needed for fabricating these devices may not be available to researchers. Hence, this study aimed to establish an alternative protocol to generate a larger, modular and reusable plant growth device based on different available resources.
Results: Root‐TRAPR (Root‐Transparent, Reusable, Affordable three‐dimensional Printed Rhizo‐hydroponic) system was successfully developed. It consists of two main parts, an internal root growth chamber and an external structural frame. The internal root growth chamber comprises a polydimethylsiloxane (PDMS) gasket, microscope slide and acrylic sheet, while the external frame is printed from a three‐dimensional (3D) printer and secured with nylon screws. To test the efficiency and applicability of the system, industrial hemp (Cannabis sativa) was grown with or without exposure to chitosan, a well‐known plant elicitor used for stimulating plant defense. Plant root morphology was detected in the system, and plant tissues were easily collected and processed to examine plant biological responses. Upon chitosan treatment, chitinase and peroxidase activities increased in root tissues (1.7‐ and 2.3‐fold, respectively) and exudates (7.2‐ and 21.6‐fold, respectively). In addition, root to shoot ratio of phytohormone contents were increased in response to chitosan. Within 2 weeks of observation, hemp plants exhibited dwarf growth in the Root‐ TRAPR system, easing plant handling and allowing increased replication under limited growing space.
Conclusion: The Root‐TRAPR system facilitates the exploration of root morphology and root exudate of C. sativa under controlled conditions and at a smaller scale. The device is easy to fabricate and applicable for investigating plant responses toward elicitor challenge. In addition, this fabrication protocol is adaptable to study other plants and can be applied to investigate plant physiology in different biological contexts, such as plant responses against biotic and abiotic stresses.
IC Legal 4
All Eyes on Europe
As new legal markets rapidly emerge across the globe, attention turns to Europe’s burgeoning market. What lessons can be learnt from those that have gone before?
Luis Merchan
Cannabis Scientist 2022
https://thecannabisscientist.com/business-profession/all-eyes-on-europe?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
https://thecannabisscientist.com/business-profession/all-eyes-on-europe?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
https://www.dutchnews.nl/news/2022/04/amsterdam-mayor-plans-to-press-ahead-with-tourist-cannabis-cafe-ban/?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
Amsterdam mayor Femke Halsema wants to press ahead with plans to close the city’s cannabis cafes, or coffee shops, to tourists, saying the move is the only option to get a grip on the local soft drugs market. Halsema told city councillors on Monday afternoon there is a ‘worrying interdependence’ between the soft and hard drug trade and that ‘money from the lucrative cannabis trade easily finds its way into hard drugs’. ‘Many of the major problems in the city are fueled by the cannabis market: from nuisance caused by drug tourism to serious crime and violence,’ she said. ‘Banning sales to tourists is a necessary intervention… and a first step towards regulation.’
Marijuana Moment April 20 2022
https://www.marijuanamoment.net/new-jersey-marijuana-sales-will-start-day-after-4-20-and-ag-says-police-can-use-while-off-duty/?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
The governor of New Jersey on Thursday announced that adults 21 and older will be able to buy marijuana from select dispensaries starting on April 21—the day after the unofficial cannabis holiday 4/20. And a new memo from the state attorney general’s office says that police can partake, too, as long as they’re off duty.
Gov. Phil Murphy (D) touted the long-awaited first round of adult-use retailer approvals from the New Jersey Cannabis Regulatory Commission (CRC), calling the action a “historic step in our work to create a new cannabis industry.”
www.ris.world
European medical cannabis company Cantourage has received two British government licenses that authorise the company to import medical cannabis to the UK.
Additionally, the company has received the required regulatory registration to prescribe medical cannabis products to clients via a new facility.
The centre has duly been named Cantourage Clinic and the company has received regulatory registration for a private tele-healthcare clinic specialised in medical cannabis. Cantourage hopes that offering an alternative to the existing UK medical cannabis clinics will broaden choice and potentially help to push down prices…
IC Medical Cannabis/Endocannabinoids Pt 1 A-D 9
Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis ‘amotivational’ hypotheses
Will Lawn & Tom P Freeman & Rebecca A Pope & Alyssa Joye & Lisa Harvey & Chandni Hindocha & Claire Mokrysz & Abigail Moss & Matthew B Wall & Michael AP Bloomfield & Ravi K Das & Celia JA Morgan & David J Nutt & H Valerie Curran
Psychopharmacology September 2016
DOI 10.1007/s00213-016-4383-x
Rationale Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. Objectives The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. Methods In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a nonintoxicated state. Results Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007). Conclusions Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.
Cannabidiol decreases motivation for cocaine in a behavioral economics paradigm but does not prevent incubation of craving in mice
Laia Alegre-Zurano, Paula Berbegal-S´aez, Miguel ´A. Lujan, Lídia Cantacorps, Ana Martín-S´anchez, Alba García-Baos, Olga Valverde Biomedicine & Pharmacotherapy 148 (2022)
DOI: 10.1016/j.biopha.2022.112708
Cocaine is a highly consumed drug worldwide which directly targets brain areas involved in reinforcement processing and motivation. Cannabidiol is a phytocannabinoid that exerts protecting effects upon cocaine-induced addictive behavior, although many questions about the mechanisms of action and the specific affected processes remain unknown. Moreover, its effects on cue-induced cocaine-craving incubation have never been addressed. The present study aimed to assess the effects of cannabidiol (20 mg/kg, i.p.) administered during the acquisition of cocaine self-administration (0.75 mg/kg/infusion) and demand task or during cocaine abstinence and craving. Moreover, we measured the alterations in expression of AMPAR subunits and ERK1/2 phosphorylation due to cannabidiol treatment or cocaine withdrawal. Our results showed that cannabidiol reduced cocaine intake when administered during the acquisition phase of the self-administration paradigm, increased behavioral elasticity and reduced motivation for cocaine in a demand task. Cannabidiol also reduced GluA1/2 ratio and increased ERK1/2 phosphorylation in amygdala. No effects over cocaine-craving incubation were found when cannabidiol was administered during abstinence. Furthermore, cocaine withdrawal induced changes in GluA1 and GluA2 protein levels in the prelimbic cortex, ventral striatum and amygdala, as well as a decrease in ERK1/2 phosphorylation in ventral striatum. Taken together, our results show that cannabidiol exerts beneficial effects attenuating the acquisition of cocaine self-administration, in which an operant learning process is required. However, cannabidiol does not affect cocaine abstinence and craving FIND PDF .
Cannabidiol but not cannabidiolic acid reduces behavioural sensitisation to methamphetamine in rats, at pharmacologically effective doses Laísa De Siqueira Umpierrez, Priscila Almeida Costa, Eden A. Michelutti, Sarah J Baracz, Melanie Sauer, Anita Jillian Turner, Nicholas A Everett, Jonathon C. Arnold, Iain S. McGregor, Jennifer L Cornish Psychopharmacology April 2022 DOI: 10.1007/s00213-022-06119-3
https://www.researchgate.net/public..._in_rats_at_pharmacologically_effective_doses
Rationale Cannabidiol (CBD) and cannabidiolic acid (CBDA) are non-psychoactive components of the cannabis plant. CBD has been well characterised to have anxiolytic and anticonvulsant activity, whereas the behavioural effects of CBDA are less clear. Preclinical and clinical data suggests that CBD has antipsychotic properties and reduces methamphetamine self-administration in rats. An animal model that is commonly used to mimic the neurochemical changes underlying psychosis and drug dependence is methamphetamine (METH) sensitisation, where repeated administration of the psychostimulant progressively increases the locomotor effects of METH. Objective The aim of this study was to determine whether CBD or CBDA attenuate METH-induced sensitisation of locomotor hyperactivity in rats. Methods Eighty-six male Sprague Dawley rats underwent METH sensitisation protocol where they were subjected to daily METH (1 mg/kg on days 2 and 8, 5 mg/kg on days 3–7; i.p.) injections for 7 days. After 21 days of withdrawal, rats were given a prior injection of CBD (0, 40 and 80 mg/kg; i.p.) or CBDA (0, 0.1, 10 and 1000 µg/kg; i.p.) and challenged with acute METH (1 mg/kg; i.p.). Locomotor activity was then measured for 60 min. Results Rats displayed robust METH sensitisation as evidenced by increased locomotor activity to METH challenge in METH-pretreated versus SAL-pretreated rats. CBD (40 and 80 mg/kg) reduced METH-induced sensitisation. There was no effect of any CBDA doses on METH sensitisation or acute METH-induced hyperactivity. Conclusion These results demonstrate that CBD, but not CBDA, reduces METH sensitisation of locomotor activity in rats at pharmacologically effective doses, thus reinforcing evidence that CBD has anti-addiction and antipsychotic properties.
Cannabinoid modulation of mother-infant interaction: is it just about milk?
Antonia Manduca, Patrizia Campolongo and Viviana Trezza
Rev. Neurosci. 2012; 23(5-6): 707–722
DOI 10.1515/revneuro-2012-0074
Mother-infant interactions are essential for proper neurobehavioral development of the offspring, and disruptions in those relationships may result in neuroendocrine, neurochemical and behavioral alterations at adulthood. The neural circuitries involved in mother-infant interactions have not been completely elucidated yet. The brain endocannabinoid system plays an essential role in prenatal and postnatal neurobehavioral development. Here, we will summarize and discuss the available findings about the role of endocannabinoids in three key aspects of mother-infant interactions in rodents: suckling, maternal behavior and separationinduced ultrasonic vocalizations (USVs). The studies reviewed here show that endocannabinoids are not only involved in suckling initiation and, therefore, in the feeding and growth of the offspring, but also regulate the emotional reactivity of rodent pups, as measured by the rate of isolation-induced USVs. Conversely, less information is available about endocannabinoid modulation of maternal behavior, and therefore more research in this direction is warranted. Indeed, since Cannabis sativa preparations are widely used by young people, including pregnant and lactating women, it is important to understand whether developmental exposure to cannabinoids interferes with mother-infant bond formation, potentially leading to neurodevelopmental alterations and increased vulnerability to psychopathology later in life.
Cannabinoids and cancer: causation, remediation, and palliation
Wayne Hall, MacDonald Christie, David Currow
Lancet Vol 6 January, 2005
http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.841.5709&rep=rep1&type=pdf
This review discusses three different associations between cannabinoids and cancer. First, it assesses evidence that smoking of cannabis preparations may cause cancers of the aerodigestive and respiratory system. There have been case reports of upper-respiratory-tract cancers in young adults who smoke cannabis, but evidence from a few epidemiological cohort studies and case-control studies is inconsistent. Second, there is mixed evidence on the effects of THC and other cannabinoids on cancers: in some in vitro and in vivo studies THC and some synthetic cannabinoids have had antineoplastic effects, but in other studies THC seems to impair the immune response to cancer. As yet there is no evidence that THC or other cannabinoids have anticancer effects in humans. Third, 9 -tetrahydrocannabinol (THC) may treat the symptoms and side-effects of cancer, and there is evidence that it and other cannabinoids may be useful adjuvant treatments that improve appetite, reduce nausea and vomiting, and alleviate moderate neuropathic pain in patients with cancer. The main challenge for the medical use of cannabinoids is the development of safe and effective methods of use that lead to therapeutic effects but that avoid adverse psychoactive effects. Furthermore, medical, legal, and regulatory obstacles hinder the smoking of cannabis for medical purposes. These very different uses of cannabinoids are in danger of being confused in public debate, especially in the USA where some advocates for the medical use of cannabinoids have argued for smoked cannabis rather than pharmaceutical cannabinoids. We review the available evidence on these three issues and consider their implications for policy. .
Cannabis and the developing brain: Insights from behavior
Viviana Trezza, Vincenzo Cuomo, Louk J.M.J. Vanderschuren
European Journal of Pharmacology 585 (2008) 441-452
DOI: 10.1016/j.ejphar.2008.01.058
The isolation and identification, in 1964, of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, opened the door to a whole new field of medical research. The exploration of the therapeutic potential of THC and other natural and synthetic cannabinoid compounds was paralleled by the discovery of the endocannabinoid system, comprising cannabinoid receptors and their endogenous ligands, which offered exciting new insights into brain function. Besides its well-known involvement in specific brain functions, such as control of movement, memory and emotions, the endocannabinoid system plays an important role in fundamental developmental processes such as cell proliferation, migration and differentiation. For this reason, changes in its activity during stages of high neuronal plasticity, such as the perinatal and the adolescent period, can have long-lasting neurobehavioral consequences. Here, we summarize human and animal studies examining the behavioral and neurobiological effects of in utero and adolescent exposure to cannabis. Since cannabis preparations are widely used and abused by young people, including pregnant women, understanding how cannabinoid compounds affect the developing brain, leading to neurobehavioral alterations or neuropsychiatric disorders later in life, is a serious health issue. In addition, since the endocannabinoid system is emerging as a novel therapeutic target for the treatment of several neuropsychiatric diseases, a detailed investigation of possible adverse effects of cannabinoid compounds on the central nervous system (CNS) of immature individuals is warranted .
Cannabis suppresses antitumor immunity by inhibiting JAK/ STAT signaling in T cells through CNR2
Xinxin Xiong, Siyu Che, Jianfei She, Hua You, Han Yan, Chao Yan, Ziqian Fan, Jianeng Zhan, Xiuyu Ca, Xingjun Don, Tiebang Kan, Wende Li and Penghui Zhou
Signal Transduction and Targeted Therapy
DOI: 10.1038/s41392-022-00918-y
https://www.nature.com/articles/s41392-022-00918-y.pdf
The combination of immune checkpoint blockade (ICB) with chemotherapy significantly improves clinical benefit of cancer treatment. Since chemotherapy is often associated with adverse events, concomitant treatment with drugs managing side effects of chemotherapy is frequently used in the combination therapy. However, whether these ancillary drugs could impede immunotherapy remains unknown. Here, we showed that Δ 9-tetrahydrocannabinol (THC), the key ingredient of drugs approved for the treatment of chemotherapy-caused nausea, reduced the therapeutic effect of PD-1 blockade. The endogenous cannabinoid anandamide (AEA) also impeded antitumor immunity, indicating an immunosuppressive role of the endogenous cannabinoid system (ECS). Consistently, high levels of AEA in the sera were associated with poor overall survival in cancer patients. We further found that cannabinoids impaired the function of tumor-specific T cells through CNR2. Using a knock-in mouse model expressing a FLAG-tagged Cnr2 gene, we discovered that CNR2 binds to JAK1 and inhibits the downstream STAT signaling in T cells. Taken together, our results unveiled a novel mechanism of the ECS-mediated suppression on T-cell immunity against cancer, and suggest that cannabis and cannabinoid drugs should be avoided during immunotherapy.
Delta‑9‑tetrahydrocannabinol reduces willingness to exert effort in women
Margaret C. Wardle · Elisa Pabon · Heather E. Webber · Harriet de Wit
Psychopharmacology
DOI: 10.1007/s00213-021-06032-1
https://link.springer.com/content/pdf/10.1007/s00213-021-06032-1.pdf
Background The use of cannabis has been clinically associated with decreased motivation to engage in normally rewarding activities. However, evidence from previous controlled studies is mixed. Method In this study, we examined the effects of acute delta-9-tetrahydrocannabinol (THC) versus placebo on a task measuring willingness to exert effort for rewards. This is a secondary analysis of a larger study examining interactions between ovarian hormones and THC. In this within-subjects study, oral THC and placebo were administered under double-blind conditions in counterbalanced order to healthy young adult (M age=24 years) women with previous cannabis experience who were not regular users. Forty subjects completed three 4-h sessions with PL, 7.5 and 15 mg THC, while an additional 18 completed only PL and 15 mg THC sessions (design abridged due to pandemic). At each session, they completed a task consisting of making repeated choices between a hard and an easy task, which were worth varying amounts of money at varying probabilities. Results THC dose-dependently decreased hard task choices (drug effect, b= −0.79, SE=0.29, z= −2.67, p<0.01), especially at moderate to high expected values of reward (drug×probability×amount interaction, b=0.77, SE=0.38, z=1.99, p=0.04). THC also slowed task performance (drug efect, b=0.01, SE=0.005, t(5.24)=2.11, p=0.04), but the effect of THC on choice was still significant after controlling for this psychomotor slowing. Conclusions These fndings support the idea that cannabis acutely reduces motivation to earn non-drug rewards. Still to be determined are the neurochemical mechanisms underlying this efect.
Development of intestinal bioavailability orediction (IBP) and phytochemical relative antitoxidant potential prediction (PRAPP) models for optimizing functional food value of Cannabis sativa (hemp).
Kimber Wise, Sophie N.B. Selby-Pham, Jamie Selby-Pham and Harsharn Gill
INTERNATIONAL JOURNAL OF FOOD PROPERTIES
2020, VOL. 23, NO. 1, 1287–1295
DOI: 10.1080/10942912.2020.1797783
Oxidative stress and inflammation (OSI) occurs naturally during many biological processes including digestion, metabolism, and exercise. While small, transient amounts of OSI are considered normal, unregulated, or chronic OSI can damage the vascular-circulatory system, which can result in chronic illnesses such as cardiovascular disease (CVD), atherosclerosis, and cancer. Antioxidant phytochemicals have the capacity to mitigate OSI through radical scavenging activity or the induction of endogenous mechanisms, but to achieve optimal reductions in OSI, the timing of antioxidant effects must occur during the onset of OSI – a concept known as ‘bio-matching.’ Additionally, the bioavailability and antioxidant capacity of active phytochemicals should be accounted for during pharmacokinetic assessments to guide bio-matching. Herein two quantitative structure–activity relationship (QSAR) predictive models are presented: the intestinal absorption prediction (IBP) model for predicting compound bioavailability (r2 = 0.93), and the phytochemical relative antioxidant potential prediction (PRAPP) model for predicting antioxidant capacity (r2 = 0.89). Application of these models to a characterized hemp meal phytochemical profile, along with established models for predicting Tmax and Tó, generated a composite antioxidant fingerprint, which predicted a peak in antioxidant activity 36 min after ingestion in liquid form. Accordingly, hemp meal-based protein powders (a common exercise supplement) should be consumed 26 min prior to completion of exercise to achieve bio-matching with the onset of exercise-induced OSI 10 min after exercise. The IBP and PRAPP models presented herein could be useful tools in understanding phytochemical complex antioxidant pharmacodynamics and in optimizing the consumption of hemp meal and other functional foods to achieve bio-matching of composite antioxidant activity with OSI profiles. .
IC Medical Cannabis/Endocannabinoids Pt 2 E-Z 15 .
Endocannabinoid System: An overview of its potential in current medical practice
Zadalla Mouslech, Vasiliki Valla
Neuro Endocrinology Letters 30(2):153-179 February 2009 https://www.researchgate.net/public...cal_practice_Neuro_Endocrinol_Lett_30_153-179 The endocannabinoid system (ECS) is a lipid signalling system, comprising of the endogenous cannabis-like ligands (endocannabinoids) anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which derive from arachidonic acid. These bind to a family of G-protein-coupled receptors, called CB1 and CB2. The cannabinoid receptor 1 (CB1R) is distributed in brain areas associated with motor control, emotional responses, motivated behaviour and energy homeostasis. In the periphery, the same receptor is expressed in the adipose tissue, pancreas, liver, GI tract, skeletal muscles, heart and the reproduction system. The CB2R is mainly expressed in the immune system regulating its functions. Endo cannabinoids are synthesized and released upon demand in a receptor-dependent way. They act as retrograde signalling messengers in GABAergic and glutamatergic synapses and as modulators of postsynaptic transmission, interacting with other neurotransmitters. Endocannabinoids are transported into cells by a specific uptake system and degraded by the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). The ECS is involved in various pathophysiological conditions in central and peripheral tissues. It is implicated in the hormonal regulation of food intake, cardiovascular, gastrointestinal, immune, behavioral, antiproliferative and mammalian reproduction functions. Recent advances have correlated the ECS with drug addiction and alcoholism. The growing number of preclinical and clinical data on ECS modulators is bound to result in novel therapeutic approaches for a number of diseases currently treated inadequately. The ECS dysregulation has been correlated to obesity and metabolic syndrome pathogenesis. Rimonabant is the first CB1 blocker launched to treat cardiometabolic risk factors in obese and overweight patients. Phase III clinical trials showed the drug's ability to regulate intra-abdominal fat tissue levels, lipidemic, glycemic and inflammatory parameters. However, safety conerns have led to its withdrawal. The role of endocannabinoids in mammalian reproduction is an emerging research area given their implication in fertilization, preimplantation embryo and spermatogenesis. The relevant preclinical data on endocannabinoid signalling open up new perspectives as a target to improve infertility and reproductive health in humans. .
Find PDF
Marijuana Dependence: Not Just Smoke and Mirrors
Divya Ramesh, Joel E. Schlosburg, Jason M. Wiebelhaus, Aron H. Lichtman
ILAR J. 2011 January ; 52(3): 295–308. doi:10.1093/ilar.52.3.295
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606907/pdf/nihms380778.pdf
Marijuana (Cannabis sativa) is the most commonly used illicit drug worldwide as well as in the Unites States. Prolonged use of marijuana or repeated administration of its primary psychoactive constituent, Δ9 -tetrahydrocannabinol (THC), can lead to physical dependence in humans and laboratory animals. The changes that occur with repeated cannabis use include alterations in behavioral, physiological, and biochemical responses. A variety of withdrawal responses occur in cannabis-dependent individuals: anger, aggression, irritability, anxiety and nervousness, decreased appetite or weight loss, restlessness, and sleep difficulties with strange dreams. But the long halflife and other pharmacokinetic properties of THC result in delayed expression of withdrawal symptoms, and because of the lack of contiguity between drug cessation and withdrawal responses the latter are not readily recognized as a clinically relevant syndrome. Over the past 30 years, a substantial body of clinical and laboratory animal research has emerged supporting the assertion that chronic exposure to cannabinoids produces physical dependence and may contribute to drug maintenance in cannabis-dependent individuals. However, no medications are approved to treat cannabis dependence and withdrawal. In this review, we describe preclinical and clinical research that supports the existence of a cannabinoid withdrawal syndrome. In addition, we review research evaluating potential pharmacotherapies (e.g., THC, a variety of antidepressant drugs, and lithium) to reduce cannabis withdrawal responses and examine how expanded knowledge about the regulatory mechanisms in the endocannabinoid system may lead to promising new therapeutic targets. .
Medicinal cannabis pilot programme (Denmark)
https://laegemiddelstyrelsen.dk/en/special/medicinal-cannabis-/medicinal-cannabis-pilot-programme/
On 1 January 2018, a medicinal cannabis pilot programme entered into force. The programme allows doctors to prescribe new types of cannabis products that were not legal in Denmark before. The pilot programme runs until 31 December 2025.
The purpose of the pilot programme is to offer patients a lawful way of testing treatment with medicinal cannabis if they have experienced no benefits from authorised medicines. That is the intention with the programme.
The products available in the pilot programme depend on the manufacturers of cannabis products. They apply for admission of cannabis products to the programme with the aim of making these products available for prescribers. The available cannabis products are therefore likely to change during the course of the pilot programme.
The currently available cannabis products can be seen on Medicine Prices, www.medicinpriser.dk.
The cannabis products included in the pilot programme are not authorised medicines – not in Denmark or any other country. Usually, the products are not tested in clinical trials like authorised medicines. So compared to authorised medicines, doctors have limited evidence of the effects and side effects. One of the implications thereof is that doctors must accept full responsibility for the prescription of a product, e.g. by determining the dose for the individual patient. They can neither consult a package leaflet nor a summary of product characteristics to assess what beneficial effects or side effects the individual patient is likely to expect
Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders
Alline Cristina Campos, Fabricio Arau´jo Moreira, Felipe Villela Gomes, Elaine Aparecida Del Bel and Francisco Silveira Guimara˜es
Phil. Trans. R. Soc. B (2012) 367, 3364–3378
doi:10.1098/rstb.2011.0389
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481531/pdf/rstb20110389.pdf
Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound D9 -tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1Amediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamidemediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARg receptors agonism, intracellular (Ca2þ) increase, etc.), on CBD behavioural effects. .
Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls
Martine Skumlien, Claire Mokrysz, Tom P. Freeman, Matthew B. Wall, Michael Bloomfield, Rachel Lees, Anna Borissova, Kat Petrilli, James Carson, Tiernan Coughlan, Shelan Ofori, Christelle Langley, Barbara J. Sahakian , H. Valerie Curran and Will Lawn
Neuropsychopharmacology Nature
https://www.nature.com/articles/s41386-022-01316-2.pdf .
Chronic use of drugs may alter the brain’s reward system, though the extant literature concerning long-term cannabis use and neural correlates of reward processing has shown mixed results. Adolescents may be more vulnerable to the adverse effects of cannabis than adults; however, this has not been investigated for reward processing. As part of the ‘CannTeen’ study, in the largest functional magnetic resonance imaging study of reward processing and cannabis use to date, we investigated reward anticipation and feedback in 125 adult (26–29 years) and adolescent (16–17 years) cannabis users (1–7 days/week cannabis use) and genderand age-matched controls, using the Monetary Incentive Delay task. Blood-oxygen-level-dependent responses were examined using region of interest (ROI) analyses in the bilateral ventral striatum for reward anticipation and right ventral striatum and left ventromedial prefrontal cortex for feedback, and exploratory whole-brain analyses. Results showed no User-Group or User-Group × Age-Group effects during reward anticipation or feedback in pre-defined ROIs. These null findings were supported by post hoc Bayesian analyses. However, in the whole-brain analysis, cannabis users had greater feedback activity in the prefrontal and inferior parietal cortex compared to controls. In conclusion, cannabis users and controls had similar neural responses during reward anticipation and in hypothesised reward-related regions during reward feedback. The whole-brain analysis revealed tentative evidence of greater fronto-parietal activity in cannabis users during feedback. Adolescents showed no increased vulnerability compared with adults. Overall, reward anticipation and feedback processing appear spared in adolescent and adult cannabis users, but future longitudinal studies are needed to corroborate this.
Neuroprotective Effects of Phytocannabinoid-Based Medicines in Experimental Models of Huntington’s Disease
Onintza Sagredo, M. Ruth Pazos, Valentina Satta, Jose ́ A. Ramos, Roger G. Pertwee, and Javier Ferna ́ndez-Ruiz
Journal of Neuroscience Research 89:1509–1518 (2011)
DOI: 10.1002/jnr.22682
We studied whether combinations of botanical extracts enriched in either D9-tetrahydrocannabinol (D9-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, provide neuroprotec- tion in rat models of Huntington’s disease (HD). We used rats intoxicated with 3-nitropropionate (3NP) that were given combinations of D9-THC- and CBD-enriched bo- tanical extracts. The issue was also studied in malonate- lesioned rats. The administration of D9-THC- and CBD- enriched botanical extracts combined in a ratio of 1:1 as in Sativex attenuated 3NP-induced GABA deficiency, loss of Nissl-stained neurons, down-regulation of Crecep- tor and IGF-1 expression, and up-regulation of calpain expression, whereas it completely reversed the reduction in superoxide dismutase-1 expression. Similar responses were generally found with other combinations of D9-THC- and CBD-enriched botanical extracts, suggesting that these effects are probably related to the antioxidant and CB and CB receptor-independent properties of both phytocannabinoids. In fact, selective antagonists for both receptor types, i.e., SR141716 and AM630, respectively, were unable to prevent the positive effects on calpain expression caused in 3NP-intoxicated rats by the 1:1 combination of D9-THC and CBD. Finally, this combina- tion also reversed the up-regulation of proinflammatory markers such as inducible nitric oxide synthase observed in malonate-lesioned rats. In conclusion, this study provides preclinical evidence in support of a beneficial effect of the cannabis-based medicine Sativex as a neuroprotective agent capable of delaying disease pro- gression in HD, a disorder that is currently poorly man- aged in the clinic, prompting an urgent need for clinical trials with agents showing positive results in preclinical studies.
Sex differences in the acute effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC)
Psychopharmacology April 2022 DOI: 10.1007/s00213-022-06135-3
Anahita Bassir Nia, Maria J. Orejarena, Leigh Flynn, Christina Luddy, Deepak Cyril D’Souza, Patrick D. Skosnik, Brian Pittman, Mohini Ranganathan
https://www.researchgate.net/public...travenous_IV_delta-9_tetrahydrocannabinol_THC
Background Cannabis is the most common illicit drug used in the USA and its use has been rising over the past decade, while the historical gap in rates of use between men and women has been decreasing. Sex differences in the effects of cannabinoids have been reported in animal models, but human studies are sparse and inconsistent. We investigated the sex differences in the acute subjective, psychotomimetic, cognitive, and physiological effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis. Methods Healthy male and female individuals, with limited exposure to cannabis, participated in a double blind, placebo-controlled study of intravenous (IV) placebo or THC at two doses (0.015 mg/kg and 0.03 mg/kg). Visual analog scale (VAS) was used to measure subjective effects, Psychotomimetic States Inventory (PSI) and the Clinician-Administered Dissociative Symptoms Scale (CADSS) were used to assess the psychotomimetic effects and perceptual alterations, respectively, and Rey Auditory Verbal Learning Task (RAVLT) was used to evaluate cognitive effects. Outcome variables were represented as the peak change from baseline for each variable, except RAVLT which was used only once per the test day after the subjective effects. Results A total of 42 individuals participated in this study. There were no significant differences between male and female participants in background characteristics. There was a significant main effect of sex on the VAS scores for THC-induced “High” (F1,38 = 4.27, p < 0.05) and a significant dose × sex interaction (F2,77 = 3.38, p < 0.05) with female participants having greater “High” scores than male participants at the lower THC dose (0.015 mg/kg). No other sex differences were observed in acute subjective, psychotomimetic, cognitive, or physiological effects of THC. Conclusion There were significant sex differences in subjective effects of feeling “High” at a lower dose of THC. However, there were no other sex-related differences in the subjective, physiological, or cognitive effects of THC.
Find PDF
https://www.frontiersin.org/articles/10.3389/fphar.2022.852029/full?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
The Endocannabinoid System in Huntington’s Disease
M.R. Pazos, O. Sagredo and J. Fernández-Ruiz
Current Pharmaceutical Design, 2008, 14, 2317-2325
DOI:10.2174/138161208785740108
The hypokinetic profile of certain cannabinoid agonists becomes these compounds as promising medicines to attenuate the hyperkinesia that characterizes the first grades of Huntington’s disease (HD) and that represents the major neurological abnormality in this disease. The fact that CB1 receptors, the receptor type involved in motor effects of cannabinoid agonists, are significantly reduced in the basal ganglia during the progression of HD represents a convincing explanation for the hyperkinesia typical of this disorder and supports the usefulness of enhancing CB1 receptor signaling in HD. However, further studies revealed that the key property that enables certain cannabinoid agonists to reduce hyperkinesia is their capability to directly activate vanilloid TRPV1 receptors. Cannabinoids may also serve to delay/arrest the progression of HD by protecting striatal projection neurons from death. Several cannabinoid agonists have been tested for this purpose in various animal models of HD, and these studies revealed that the major characteristics that enable cannabinoids to provide neuroprotection are three: (i) a reduction in inflammatory events exerted through activating CB2 receptors located in glial cells; (ii) a normalization of glutamate homeostasis, then limiting excitotoxicity, an effect that would be exerted through CB1 receptors; and (iii) an antioxidant effect exerted by cannabinoid receptor-independent mechanisms. The changes experienced by the endocannabinoid signaling system during the striatal degeneration support this neuroprotective effect, particularly the up-regulatory responses proved by CB2 receptors in glial cells recruited at lesioned sites. The present article will review the neurochemical and pharmacological bases that sustain the importance of the endocannabinoid system in the pathophysiology of HD, trying to collect the present information and the future lines for research on the therapeutic potential of this system in this disorder.
The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract
Federico Massa . Martin Storr . Beat Lutz
J Mol Med (2005) 83: 944–954
DOI 10.1007/s00109-005-0698-5
Numerous investigations have recently demonstrated the important roles of the endocannabinoid system in the gastrointestinal (GI) tract under physiological and pathophysiological conditions. In the GI tract, cannabinoid type 1 (CB1) receptors are present in neurons of the enteric nervous system and in sensory terminals of vagal and spinal neurons, while cannabinoid type 2 receptors are located in immune cells. Activation of CB1 receptors was shown to modulate several functions in the GI tract, including gastric secretion, gastric emptying and intestinal motility. Under pathophysiological conditions induced experimentally in rodents, the endocannabinoid system conveys protection to the GI tract (e.g. from inflammation and abnormally high gastric and enteric secretions). Such protective activities are largely in agreement with anecdotal reports from folk medicine on the use of Cannabis sativa extracts by subjects suffering from various GI disorders. Thus, the endocannabinoid system may serve as a potentially promising therapeutic target against different GI disorders, including frankly inflammatory bowel diseases (e.g. Crohn’s disease), functional bowel diseases (e.g. irritable bowel syndrome) and secretion- and motilityrelated disorders. As stimulation of this modulatory system by CB1 receptor agonists can lead to unwanted psychotropic side effects, an alternative and promising avenue for therapeutic applications resides in the treatment with CB1 receptor agonists that are unable to cross the blood–brain barrier, or with compounds that inhibit the degradation of endogenous ligands (endocannabinoids) of CB1 receptors, hence prolonging the activity of the endocannabinoid system.
The Medical Geography of Cannabinoid Botanicals in Washington State: Access, Delivery, and Distress
Sunil Kumar Aggarwal
University of Washington 2008
http://www.cannabinologist.org/Documents/SunilAggarwal_Dissertation.pdf
Though rendered dormant by a post-1937 Cannabis sativa L. prohibition, the emerging field of cannabinoid medicine is growing in the United States as ever greater numbers of physicians become educated about the physiologic importance of the endogenous cannabinoid system and about the wide safety margins and broad clinical efficacies of cannabinoid drugs, available in both purely botanical and purely chemical varieties and useful for managing pain and other conditions in the growing chronically and critically ill patient population. Research presented here is focused on medical access and delivery of cannabinoid botanicals in Washington State and seeks to map the geography of this developing cannabinoid medical care system by taking medical geographic “snapshots” of two purposefully chosen locations: a rural clinic site in Washington State where patients currently access cannabinoid botanicals for medical use in the treatment of chronic pain syndromes with acceptable safety under medical supervision and another site where qualifying patients are delivered environmentallyculled cannabinoid botanicals. At the former site, retrospective chart reviews were conducted with 139 patients with chronic pain, and at the latter site, a convenience sample of 37 qualifying patients delivered a monoclonal lot of cannabinoid botanical medicine were prospectively studied using standard and tailored survey instruments. A political ecology of disease approach was employed to rationalize and depathologize patients’ mental distress at potentially facing possession-related legal problems due to their consumption of the still-contraband biota. Results provide quantitative and qualitative insight into the frail health status in both samples of qualifying patients and give a grounded understanding of the lengths that patients and care providers go, despite multiple hurdles, to access and deliver treatment with cannabinoid botanicals that relieves patients’ diverse symptoms and improves their health-related quality-of life. .
The Medicalization of Cannabis
Edited by S M Crowther, L A Reynolds and E M Tansey
The transcript of a Witness Seminar held by the Wellcome Trust Centre for the History of Medicine at UCL, London, on 24 March 2009
https://qmro.qmul.ac.uk/xmlui/bitst...icalizationofCannabis2010FINAL.pdf?sequence=2
CONTENTS Illustrations and credits v
Abbreviations vii
Witness Seminars: Meetings and publications; Acknowledgements E M Tansey, L A Reynolds and S M Crowther ix
Introduction Leslie Iversen xix
Transcript Edited by S M Crowther, L A Reynolds and E M Tansey 1
Appendix 1 Diagrams of the structures of some major plant cannabinoids and of certain structurally related synthetic cannabinoids 73
References 75
Biographical notes 89
Index 97
The medical use of cannabis has a very long history; it was used for thousands of years in Indian and other Asian medicine and was first introduced to the west in the mid-nineteenth century by a brilliant young doctor, W B O’Shaughnessy, returning to England after service in India. Cannabis was taken up enthusiastically by physicians in Europe and the US and was widely used for almost a hundred years until it fell out of favour as new and more easily standardized medicines became available and government regulations were imposed. Tincture of cannabis finally left the British Pharmacopoeia in the mid-1970s.
This Witness Seminar, however, was focused not on this early history but on the resurgence of interest in medical cannabis that has occurred in the past few decades. It brought together a group of people with diverse expertise who had witnessed at first hand the development of this field. Although the seminar did not deal at all with the recreational use of cannabis, it is impossible to consider the history of medical cannabis without considering the impact that the rapid growth of the illicit recreational use of the drug in the latter part of the twentieth century has had. The ‘cannabis wars’ have been fought between those who believe it to be harmless and medically useful, and those who see it as a danger to health and to society without any legitimate medical use. For many years the stigmatization of cannabis had a negative influence on the availability of research funding and promoted reluctance on the part of doctors and pharmaceutical companies to be involved in research on the medical uses of cannabis.
J Arthroplasty April 2022 doi: 10.1016/j.arth.2022.03.081
Background: Multimodal analgesia has become the standard of care for pain management following total knee arthroplasty (TKA). Cannabidiol (CBD) is increasingly utilized in the postoperative period. The purpose of this study was to analyze the analgesic benefits of topical CBD following primary TKA.
Methods: In this randomized double-blinded placebo-controlled trial, 80 patients undergoing primary unilateral TKA applied topical CBD (CBD; n=19), essential oil (EO; n=21), CBD and essential oil (CBD+EO; n=21), or placebo (PLA; n=19) thrice daily around the knee for two weeks postoperatively. This supplemented a standardized multimodal analgesic protocol. Outcomes included visual analog scale (VAS) pain and numeric rating scale (NRS) sleep scores (collected on postoperative day [POD] 0, 1, 2, 7, 14, 42), and cumulative postoperative opioid use (42 days).
Results: Demographic characteristics were similar among the four cohorts. Preoperative VAS and NRS scores were similar among groups. The CBD cohort had a higher mean VAS pain score on POD 2 compared to the EO cohort (CBD: 69.9 ± 19.3 vs. EO: 51.0 ± 18.2; p=0.013). No significant differences existed for VAS scores at other times, and no significant differences were observed for postoperative NRS sleep scores or postoperative opioid use at any time point.
Conclusions: Utilization of topical CBD in supplement to multimodal analgesia did not reduce pain or opioid consumption, or improve sleep scores following TKA. These results suggest the local effects of topical CBD are not beneficial for providing additional pain relief after TKA.
Find PDF
April 21
2 in IC Cannabinoids
6 in IC Cannabis Analysis
5 in IC Cannabis Botany
4 in IC Legal
9 in IC Medical Cannabis/Endocannabinoids Pt 1 A-D
15 in IC Medical Cannabis/Endocannabinoids Pt 2 E-Z
IC Cannabinoids 2
Associations between cannabinoids and growth stages of twelve industrial hemp cultivars grown outdoors in Atlantic Canada
Nada Hammami, Jean-Pierre Privé, David L Joly, Gaétan Moreau Industrial Crops and Products 172(29):113997 Nov 2021 DOI: 10.1016/j.indcrop.2021.113997
https://www.researchgate.net/public...p_cultivars_grown_outdoors_in_Atlantic_Canada
Industrial hemp is increasingly grown and harvested for its cannabinoids of pharmaceutical interest. These compounds are generally obtained from plants harvested at maturity but not all cannabinoids are present or abundant during the last stage of hemp development. This study examined intraspecific cannabinoid variability during ontogenic development of hemp to identify growth stages and cultivars that optimize production of specific compounds. The cannabinoid content of twelve commercial industrial hemp (Cannabis sativa L. subsp. sativa) cultivars at three growth stages (i.e., flowering, grain filling and maturity) was determined by high performance liquid chromatography in an experimental field in Cocagne, New Brunswick, Canada. Most cannabinoids in acidic or neutral form were more abundant at maturity. However, cannabigerolic acid, a precursor to all acidic and neutral forms of cannabinoids mentioned in our study, was more abundant during the grain-filling stage. In contrast, cannabichromene was associated with the flowering stage and found in greater abundances in grain cultivars than in dual-purpose cultivars. The cultivar Katani exhibited higher concentrations of most cannabinoids while the cultivars Ferimon, Altair and Anka exhibited higher concentrations of cannabinoid acidic precursors. The current study could help optimize the targeted production of cannabinoids at specific growth stages and to identify the chemical phenotype of different hemp cultivars. .
Cannabinoid modulation of mother-infant interaction: is it just about milk?
Antonia Manduca, Patrizia Campolongo and Viviana Trezza
Rev. Neurosci. 2012; 23(5-6): 707–722
DOI 10.1515/revneuro-2012-0074
Mother-infant interactions are essential for proper neurobehavioral development of the offspring, and disruptions in those relationships may result in neuroendocrine, neurochemical and behavioral alterations at adulthood. The neural circuitries involved in mother-infant interactions have not been completely elucidated yet. The brain endocannabinoid system plays an essential role in prenatal and postnatal neurobehavioral development. Here, we will summarize and discuss the available findings about the role of endocannabinoids in three key aspects of mother-infant interactions in rodents: suckling, maternal behavior and separationinduced ultrasonic vocalizations (USVs). The studies reviewed here show that endocannabinoids are not only involved in suckling initiation and, therefore, in the feeding and growth of the offspring, but also regulate the emotional reactivity of rodent pups, as measured by the rate of isolation-induced USVs. Conversely, less information is available about endocannabinoid modulation of maternal behavior, and therefore more research in this direction is warranted. Indeed, since Cannabis sativa preparations are widely used by young people, including pregnant and lactating women, it is important to understand whether developmental exposure to cannabinoids interferes with mother-infant bond formation, potentially leading to neurodevelopmental alterations and increased vulnerability to psychopathology later in life.
IC Cannabis Analysis 6
A Comprehensive Phytochemical Analysis of Terpenes, Polyphenols and Cannabinoids, and Micromorphological Characterization of 9 Commercial Varieties of Cannabis sativa L.
Eugenia Mazzara, Jacopo Torresi, Gelsomina Fico, Alessio Papini, Nicola Kulbaka, Stefano Dall’Acqua, Stefania Sut, Stefania Garzoli, Ahmed M. Mustafa, Loredana Cappellacci, Dennis Fiorini, Filippo Maggi, Claudia Giuliani And Riccardo Petrell
Plants 2022New hemp (Cannabis sativa L.) strains developed by crossbreeding selected varieties represent a novel research topic worthy of attention and investigation. This study focused on the phytochemical characterization of nine hemp commercial cultivars. Hydrodistillation was performed in order to collect the essential oils (EO), and also the residual water and deterpenated biomass. The volatile fraction was analyzed by GC-FID, GC-MS, and SPME-GC-MS, revealing three main chemotypes. The polyphenolic profile was studied in the residual water and deterpenated biomass by spectrophotometric assays, and HPLC-DAD-MSn and 1H-NMR analyses. The latter were employed for quali–quantitative determination of cannabinoids in the deterpenated material in comparison with the one not subjected to hydrodistillation. In addition, the glandular and non-glandular indumentum of the nine commercial varieties was studied by means of light microscopy and scanning electron microscopy in the attempt to find a possible correlation with the phytochemical and morphological traits. The EO and residual water were found to be rich in monoterpene and sesquiterpene hydrocarbons, and flavonol glycosides, respectively, while the deterpenated material was found to be a source of neutral cannabinoids. The micromorphological survey allowed us to partly associate the phytochemistry of these varieties with the hair morphotypes. This research sheds light on the valorization of different products from the hydrodistillation of hemp varieties, namely, essential oil, residual water, and deterpenated biomass, which proved to be worthy of exploitation in industrial and health applications. .
Cannabinoid Quantitation via Rugged and Adaptable HPLC/UHPLC Method Development
The Analytical Scientist & phenomenex 04/23/2020 WebVideo
https://thecannabisscientist.com/webinar/cannabinoid-quantitation-via-rugged-and-adaptable-hplc/uhplc-method-development?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
https://view6.workcast.net/register?cpak=8256969521182128
https://view6.workcast.net/registerthanks?regtracker=ftxfw1yaOQjOZY6KSLd1YcuAb4nsm56VJU18/grmNy1DZOW1gogLZIagxVWSojlk
https://view6.workcast.net/AuditoriumAuthenticator.aspx?cpak=8256969521182128&pak=7298980096326304
Potency testing demands in the cannabis industry have exploded and are continuing to expand in product formulations, applications, and plant cultivations. Of the hundreds of known cannabinoid molecules, six have been of primary interest to quantitate (THC, THC-A, CBD, CBD-A, CBG, and CBG-A). With various regulations, such as the Farm Bill, distinguishing between Marijuana and Hemp through levels of intoxicating cannabinoids, specific and accurate quantitation of these cannabinoids is ever more critical and even more challenging with a rising number and level of minor cannabinoids potentially present from chemical reactions or novel cultivars. Along with the sheer number of potentially interfering cannabinoids, their chromatographic profiles are a challenge to maintain as their retention profiles can have significant shifts from minute changes in common chromatographic conditions. Here we’ll cover the key underlying chromatographic factors to ensure robust and rugged potency method development that can be adapted readily to accommodate the dynamic landscape.
Learning Objectives
Mobile phase factors applied to method accuracy and ruggedness.
Instrument and method transfer considerations in robustness.
Critical cannabinoids resolved chromatographically.
Cannabis Analysis Challenges: One Size Does Not Fit All
07/30/2020 Cannabis Scientist & UCT WebVideo
https://thecannabisscientist.com/webinar/cannabis-analysis-challenges-one-size-does-not-fit-all?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS%20Newsletter%20Week%2016%202022&utm_medium=email
https://view6.workcast.net/register?cpak=3955142647254094
https://view6.workcast.net/registerthanks?regtracker=j8q0metdvHs1w+tZOCg6WorO7ckn0BJLc4oJQaDkWcrdBCP+2G3roRneJTvV1v8H
https://view6.workcast.net/AuditoriumAuthenticator.aspx?cpak=3955142647254094&pak=4190894796166546
UCT and AltaSci have partnered together in presenting the vast analytical challenges faced in the cannabis and hemp marketplace. Specifically, the diversity of matrix encountered does not afford a one size fits all approach. Today’s webinar will explore various sample clean-up options for flower, edibles, and concentrates and will also showcase how each matrix requires its own tailor-made extraction to ensure overall data accuracy and repeatability. By tapping on UCT’s diverse sorbent chemistry offerings in addition to AltaSci’s experience in full pharmaceutical grade testing for 75% of the licensed production facilities in Connecticut, an exhaustive cannabis analysis will be co-presented.Learning Objectives of Webinar
Sample clean-up is highly dependent upon the matrix of analysis.
Different sorbent chemistries can provide varying levels of sample clean-up and analyte recovery.
UCT offers a diverse sorbent chemistry arsenal to work with labs in solving their cannabis challenges.
Moisture Content Determination in Hemp and Hemp Flower
The Cannabis Scientist. & METTLER TOLEDO 11/16/2020 Webvideo
https://thecannabisscientist.com/webinar/moisture-content-determination-in-hemp-and-hemp-flower?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
https://view6.workcast.net/register...F84nwIAFgoRQ5rb0NBG2tKifZdeUmS37SdvIwCej7of2K
https://view6.workcast.net/AuditoriumAuthenticator.aspx?cpak=5312466848601485&pak=6239340224033044
Moisture content determination techniques and their implication on potency based on dry weight calculations in cannabis and hemp industry. Discussion of use cases for Karl Fischer Titration, Thermogravimetric Halogen Moisture Analysis and Conventional Loss on Drying (drying oven and balance).Learning Objectives:
Moisture content determination techniques
Use cases for various instruments
Not So Volatile
Low VOC emissions from indoor cannabis cultivation facilities – good news for people and the planet?Margot Lespade | 04/20/2022
https://thecannabisscientist.com/testing-processing/not-so-volatile?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS%20Newsletter%20Week%2016%202022&utm_medium=email
As cannabis legalization becomes increasingly common, there is growing concern over its environmental impact, particularly in indoor cultivation settings. In an effort to explore these effects, researchers from the Colorado Department of Public Health and Environment (CDPHE) examined air quality samples from three indoor cultivation facilities in Colorado (1). Despite these facilities’ high nuisance odors, they found the volatile organic compounds (VOCs) emissions rate to be low – even at large cultivation facilities. We spoke with the paper’s first author, Kaitlin Urso, to find out more.Structure elucidation of the tetrahydrocannabinol complex with randomly methylated -cyclodextrin
Arno Hazekamp, Rob Verpoorte
european journal of pharmaceutical sciences 29 (2006) 340–347
Doi: 10.1016/j.ejps.2006.07.001
The low aqueous solubility of the bioactive cannabinoid tetrahydrocannabinol (THC) is a serious obstacle for the development of more efficient administration forms. In this study the aqueous solubility of THC was tested in the presence of -, - and -CD, and randomly methylated -CD (RAMEB). It was found that only RAMEB was able to increase the aqueous solubility of THC to a significant level. A THC concentration of about 14mg/ml was reached by using a 24% (187mM) RAMEB solution, which means an increase in solubility of four orders of magnitude. The resulting THC/RAMEB complex was investigated through phase-solubility analysis, complemented by 1H NMR, NOESY- and UV-studies in order to obtain details on the stoichiometry, geometry and thermodynamics of the complexation. The binding ratio of THC to CD was found to be 2:1, with the second THC molecule bound by non-inclusion interactions. Based on the obtained results a model for the complex structure is presented. Stability of the complex under laboratory room conditions was tested up to 8 weeks. Results show that complexation with RAMEB seems to be promising for the development of waterbased THC formulations
IC Cannabis Botany 5 .
Associations between cannabinoids and growth stages of twelve industrial hemp cultivars grown outdoors in Atlantic Canada
Nada Hammami, Jean-Pierre Privé, David L Joly, Gaétan Moreau Industrial Crops and Products 172(29):113997 Nov 2021 DOI: 10.1016/j.indcrop.2021.113997
https://www.researchgate.net/public...p_cultivars_grown_outdoors_in_Atlantic_Canada
Industrial hemp is increasingly grown and harvested for its cannabinoids of pharmaceutical interest. These compounds are generally obtained from plants harvested at maturity but not all cannabinoids are present or abundant during the last stage of hemp development. This study examined intraspecific cannabinoid variability during ontogenic development of hemp to identify growth stages and cultivars that optimize production of specific compounds. The cannabinoid content of twelve commercial industrial hemp (Cannabis sativa L. subsp. sativa) cultivars at three growth stages (i.e., flowering, grain filling and maturity) was determined by high performance liquid chromatography in an experimental field in Cocagne, New Brunswick, Canada. Most cannabinoids in acidic or neutral form were more abundant at maturity. However, cannabigerolic acid, a precursor to all acidic and neutral forms of cannabinoids mentioned in our study, was more abundant during the grain-filling stage. In contrast, cannabichromene was associated with the flowering stage and found in greater abundances in grain cultivars than in dual-purpose cultivars. The cultivar Katani exhibited higher concentrations of most cannabinoids while the cultivars Ferimon, Altair and Anka exhibited higher concentrations of cannabinoid acidic precursors. The current study could help optimize the targeted production of cannabinoids at specific growth stages and to identify the chemical phenotype of different hemp cultivars. . .
Can DEA-backed cannabis growers strike gold via drug development?
mar Sacirbey MJBizDaily
https://mjbizdaily.com/dea-backed-cannabis-growers-seek-to-strike-gold-via-drug-development/?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=emailThe cannabis industry hit a possible milestone in March when Bright Green Corp., a Florida company with “conditional” approval from the U.S. Drug Enforcement Administration to grow marijuana for research purposes, applied to list on the Nasdaq stock exchange.
If successful, Bright Green would become the first U.S. plant-touching company to list on a major U.S. stock exchange.
But the move also highlights the lofty – some say unrealistic – financial ambitions of such companies.
And it raises the question of whether a business model based on DEA approval is realistic from a financial standpoint.
The five entities registered with the DEA as “Bulk Manufacturer Marihuana Growers” are allowed to grow and sell marijuana flower and extract to researchers registered with the federal agency.
Those researchers can be at universities, pharmaceutical companies and other entities.
The University of Mississippi received the first DEA cultivation registration in 1968, while four more entities received registrations in 2021.
Three of the other four entities that have secured DEA approval are private companies, while the Scottsdale Research Institute in Cave Creek, Arizona, is a nonproft focused on determining “the general medical safety and efficacy of cannabis and cannabis products.”
Other entities, such as Fort Lauderdale-based Bright Green, are vying for additional registrations, although it’s not clear if or when the DEA will issue any more.
In addition to making money through the cultivation of marijuana for scientific research, at last three of the DEA-approved companies hope to further capitalize on cannabis-based drug development.
They are:
Biopharmaceutical Research Co., in Castroville, California.
Groff North America, in Red Lion, Pennsylvania.
Royal Emerald Pharmaceuticals, in Desert Hot Springs, California.
How can such drug development be a money winner?
The answer? By partnering with pharmaceutical companies and multistate operators to develop drugs approved by the U.S. Food and Drug Administration that could be sold by prescription or even over the counter.
Each company attained DEA bulk cannabis manufacturing registration in 2021.
“Conceptually, the opportunity is phenomenal. If you total up all the pharmaceutical sales for the indications that cannabis can address, like sleep pain, nausea, etc., it’s a $330 billion-a-year market. There’s lots and lots of activity to be had in this pharmaceutical facilitator area,” said Joe Grzyb, CEO of Groff North America.
But he added: “You have to be patient, because it takes several years to get through the FDA process.”
Doubts over DEA-based business model
Sue Sisley, head of the Scottsdale Research Institute – which is among the five DEA cannabis cultivation registrants – said business models based on the DEA registrations are bound to fail.
“The entities who are trying to build a business model around these few research registrations won’t be successful. The demand for research cannabis is minimal,” Sisley said.
“This is not a lucrative business model and never will be. It takes over 10 years to develop drugs that get FDA approval – and is massively more complicated when it comes to agricultural products that have complex chemical composition with tons of different bioactive molecules.”
The University of Mississippi received the first DEA permit to grow cannabis for research in 1968.
Effect of Timing of Ethephon Treatment on the Formation of Female Flowers and Seeds from Male Plant of Hemp (Cannabis sativa L.
Youn-Ho Moon, Yoon Jeong Lee, Sung Cheol Koo, Mok Hur, Yun Chan Huh, Jae-Ki Chang and Woo Tae Park
Korean J. Plant Res. 33(6):682-688(2020)
DOI: 10.7732/kjpr.2020.33.6.682
http://203.250.217.22/article/JAKO202034965719736.pdf
Hemp (Cannabis sativa L.) is a dioecious plant, although monoecious plants are bred in some cultivars for fiber or seed production. Recently, hemp has received attention for medicinal use with some cannabinoids, including cannabidiol. Self-fertilization for breeding inbred lines is difficult because of dioeciousness and anemophily in hemp. This experiment was conducted to develop a self-fertilization method by forming female flowers and seeds from male plants of dioecious hemp. To induce the formation of female flowers on male plants, 500 ㎎ L-1 of ethephon was sprayed on plants at soon, seven and fourteen days after primordia formation. The plant ratio of female flowers formation and the number of harvested seeds were increased by ethephon treatment. Female flowers of male plants have 5 stigmas in contrast to the dual stigma of female 1plants. Male plant seeds were lighter and smaller than those from female plants. Although the germination rate was lower than that of normal seeds from female plants, the seeds from male plants germinated to grow seedlings. Thus, we suggest that hemp plants should be treated with ethephon at soon after primordia formation to induce the formation of more female flowers on the male plants. .
INFLUENCE OF STORAGE AND MIXING FACTORS ON THE BIOLOGICAL ACTIVITY OF SILVER THIOSULFATE
ARTHUR C. CAMERON, ROYAL D. HEINS and HAROLD N. FONDA
DOI: 10.1016/0304-4238(85)90009-3
Scientia Horticulturae, 26 (1985) 167--174
Silver thiosulfate (STS) complex stability and degradation during formulation and storage were monitored indirectly by determining the effectiveness of treatment solutions in retarding flower petal abscission in geraniums (Pelargonium hortorum Baily). Freshly prepared solutions composed of Ag+:S2032- ratios from1:1 to 1:16 at constant silver concentration were all equally effective. There were no differences in effectiveness when a Ag+:S2032- solution of ratio 1:4 was formulated at 5, 25 or 50°C, when prepared at pH 4.01, 7.0 or 10.0, or when prepared in the presence of 10 mM KC1, Na2CO3, Ca(NO3) 2 or MgSO~. The ability of solutions to retard abscission was reduced when Ag + was substantially in excess of $2032-. Rapid mixing of AgNO3 and Na2S~O3 solutions yielded effectiw~ solutions, independent of mixing order. Complete loss of activity was observed when solutions were stored in contact with either tin or galvanized metal for 5 days, whereas there was no loss in activity after 3 months' storage in plastic or glass at 2°C. These results indicate that currently recommended formulation procedures are unnecessarily stringent, and that long-term cold storage of prepared STS solutions is feasible.
Root-TRAPR: a modular plant growth device to visualize root development and monitor growth parameters, as applied to an elicitor response of Cannabis sativa
Pipob Suwanchaikasem, Alexander Idnurm, Jamie Selby‐Pham, Robert Walker and Berin A. Boughton
Suwanchaikasem et al. Plant Methods (2022) 18:46
DOI: 10.1186/s13007-022-00875-1
https://www.researchgate.net/public...icitor_response_of_Cannabis_sativa/references
Background: Plant growth devices, for example, rhizoponics, rhizoboxes, and ecosystem fabrication (EcoFAB), have been developed to facilitate studies of plant root morphology and plant‐microbe interactions in controlled labora‐ tory settings. However, several of these designs are suitable only for studying small model plants such as Arabidopsis thaliana and Brachypodium distachyon and therefore require modification to be extended to larger plant species like crop plants. In addition, specific tools and technical skills needed for fabricating these devices may not be available to researchers. Hence, this study aimed to establish an alternative protocol to generate a larger, modular and reusable plant growth device based on different available resources.
Results: Root‐TRAPR (Root‐Transparent, Reusable, Affordable three‐dimensional Printed Rhizo‐hydroponic) system was successfully developed. It consists of two main parts, an internal root growth chamber and an external structural frame. The internal root growth chamber comprises a polydimethylsiloxane (PDMS) gasket, microscope slide and acrylic sheet, while the external frame is printed from a three‐dimensional (3D) printer and secured with nylon screws. To test the efficiency and applicability of the system, industrial hemp (Cannabis sativa) was grown with or without exposure to chitosan, a well‐known plant elicitor used for stimulating plant defense. Plant root morphology was detected in the system, and plant tissues were easily collected and processed to examine plant biological responses. Upon chitosan treatment, chitinase and peroxidase activities increased in root tissues (1.7‐ and 2.3‐fold, respectively) and exudates (7.2‐ and 21.6‐fold, respectively). In addition, root to shoot ratio of phytohormone contents were increased in response to chitosan. Within 2 weeks of observation, hemp plants exhibited dwarf growth in the Root‐ TRAPR system, easing plant handling and allowing increased replication under limited growing space.
Conclusion: The Root‐TRAPR system facilitates the exploration of root morphology and root exudate of C. sativa under controlled conditions and at a smaller scale. The device is easy to fabricate and applicable for investigating plant responses toward elicitor challenge. In addition, this fabrication protocol is adaptable to study other plants and can be applied to investigate plant physiology in different biological contexts, such as plant responses against biotic and abiotic stresses.
IC Legal 4
All Eyes on Europe
As new legal markets rapidly emerge across the globe, attention turns to Europe’s burgeoning market. What lessons can be learnt from those that have gone before?
Luis Merchan
Cannabis Scientist 2022
https://thecannabisscientist.com/business-profession/all-eyes-on-europe?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
https://thecannabisscientist.com/business-profession/all-eyes-on-europe?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
Amsterdam mayor plans to press ahead with tourist cannabis cafe ban
April 12, 2022https://www.dutchnews.nl/news/2022/04/amsterdam-mayor-plans-to-press-ahead-with-tourist-cannabis-cafe-ban/?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
Amsterdam mayor Femke Halsema wants to press ahead with plans to close the city’s cannabis cafes, or coffee shops, to tourists, saying the move is the only option to get a grip on the local soft drugs market. Halsema told city councillors on Monday afternoon there is a ‘worrying interdependence’ between the soft and hard drug trade and that ‘money from the lucrative cannabis trade easily finds its way into hard drugs’. ‘Many of the major problems in the city are fueled by the cannabis market: from nuisance caused by drug tourism to serious crime and violence,’ she said. ‘Banning sales to tourists is a necessary intervention… and a first step towards regulation.’
Marijuana Moment April 20 2022
https://www.marijuanamoment.net/new-jersey-marijuana-sales-will-start-day-after-4-20-and-ag-says-police-can-use-while-off-duty/?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
The governor of New Jersey on Thursday announced that adults 21 and older will be able to buy marijuana from select dispensaries starting on April 21—the day after the unofficial cannabis holiday 4/20. And a new memo from the state attorney general’s office says that police can partake, too, as long as they’re off duty.
Gov. Phil Murphy (D) touted the long-awaited first round of adult-use retailer approvals from the New Jersey Cannabis Regulatory Commission (CRC), calling the action a “historic step in our work to create a new cannabis industry.”
UK – Cannabis firm launches UK clinic following prescription license allocation
Cantourage has appointed cannabis prescribers and is now officially operational via a new centre
UK - Cannabis firm launches UK clinic following prescription license allocation - RIS.WORLD
European medical cannabis company Cantourage has received two British government licenses that authorise the company to import medical
www.ris.world
Additionally, the company has received the required regulatory registration to prescribe medical cannabis products to clients via a new facility.
The centre has duly been named Cantourage Clinic and the company has received regulatory registration for a private tele-healthcare clinic specialised in medical cannabis. Cantourage hopes that offering an alternative to the existing UK medical cannabis clinics will broaden choice and potentially help to push down prices…
IC Medical Cannabis/Endocannabinoids Pt 1 A-D 9
Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis ‘amotivational’ hypotheses
Will Lawn & Tom P Freeman & Rebecca A Pope & Alyssa Joye & Lisa Harvey & Chandni Hindocha & Claire Mokrysz & Abigail Moss & Matthew B Wall & Michael AP Bloomfield & Ravi K Das & Celia JA Morgan & David J Nutt & H Valerie Curran
Psychopharmacology September 2016
DOI 10.1007/s00213-016-4383-x
Rationale Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. Objectives The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. Methods In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a nonintoxicated state. Results Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007). Conclusions Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.
Cannabidiol decreases motivation for cocaine in a behavioral economics paradigm but does not prevent incubation of craving in mice
Laia Alegre-Zurano, Paula Berbegal-S´aez, Miguel ´A. Lujan, Lídia Cantacorps, Ana Martín-S´anchez, Alba García-Baos, Olga Valverde Biomedicine & Pharmacotherapy 148 (2022)
DOI: 10.1016/j.biopha.2022.112708
Cocaine is a highly consumed drug worldwide which directly targets brain areas involved in reinforcement processing and motivation. Cannabidiol is a phytocannabinoid that exerts protecting effects upon cocaine-induced addictive behavior, although many questions about the mechanisms of action and the specific affected processes remain unknown. Moreover, its effects on cue-induced cocaine-craving incubation have never been addressed. The present study aimed to assess the effects of cannabidiol (20 mg/kg, i.p.) administered during the acquisition of cocaine self-administration (0.75 mg/kg/infusion) and demand task or during cocaine abstinence and craving. Moreover, we measured the alterations in expression of AMPAR subunits and ERK1/2 phosphorylation due to cannabidiol treatment or cocaine withdrawal. Our results showed that cannabidiol reduced cocaine intake when administered during the acquisition phase of the self-administration paradigm, increased behavioral elasticity and reduced motivation for cocaine in a demand task. Cannabidiol also reduced GluA1/2 ratio and increased ERK1/2 phosphorylation in amygdala. No effects over cocaine-craving incubation were found when cannabidiol was administered during abstinence. Furthermore, cocaine withdrawal induced changes in GluA1 and GluA2 protein levels in the prelimbic cortex, ventral striatum and amygdala, as well as a decrease in ERK1/2 phosphorylation in ventral striatum. Taken together, our results show that cannabidiol exerts beneficial effects attenuating the acquisition of cocaine self-administration, in which an operant learning process is required. However, cannabidiol does not affect cocaine abstinence and craving FIND PDF .
Cannabidiol but not cannabidiolic acid reduces behavioural sensitisation to methamphetamine in rats, at pharmacologically effective doses Laísa De Siqueira Umpierrez, Priscila Almeida Costa, Eden A. Michelutti, Sarah J Baracz, Melanie Sauer, Anita Jillian Turner, Nicholas A Everett, Jonathon C. Arnold, Iain S. McGregor, Jennifer L Cornish Psychopharmacology April 2022 DOI: 10.1007/s00213-022-06119-3
https://www.researchgate.net/public..._in_rats_at_pharmacologically_effective_doses
Rationale Cannabidiol (CBD) and cannabidiolic acid (CBDA) are non-psychoactive components of the cannabis plant. CBD has been well characterised to have anxiolytic and anticonvulsant activity, whereas the behavioural effects of CBDA are less clear. Preclinical and clinical data suggests that CBD has antipsychotic properties and reduces methamphetamine self-administration in rats. An animal model that is commonly used to mimic the neurochemical changes underlying psychosis and drug dependence is methamphetamine (METH) sensitisation, where repeated administration of the psychostimulant progressively increases the locomotor effects of METH. Objective The aim of this study was to determine whether CBD or CBDA attenuate METH-induced sensitisation of locomotor hyperactivity in rats. Methods Eighty-six male Sprague Dawley rats underwent METH sensitisation protocol where they were subjected to daily METH (1 mg/kg on days 2 and 8, 5 mg/kg on days 3–7; i.p.) injections for 7 days. After 21 days of withdrawal, rats were given a prior injection of CBD (0, 40 and 80 mg/kg; i.p.) or CBDA (0, 0.1, 10 and 1000 µg/kg; i.p.) and challenged with acute METH (1 mg/kg; i.p.). Locomotor activity was then measured for 60 min. Results Rats displayed robust METH sensitisation as evidenced by increased locomotor activity to METH challenge in METH-pretreated versus SAL-pretreated rats. CBD (40 and 80 mg/kg) reduced METH-induced sensitisation. There was no effect of any CBDA doses on METH sensitisation or acute METH-induced hyperactivity. Conclusion These results demonstrate that CBD, but not CBDA, reduces METH sensitisation of locomotor activity in rats at pharmacologically effective doses, thus reinforcing evidence that CBD has anti-addiction and antipsychotic properties.
Cannabinoid modulation of mother-infant interaction: is it just about milk?
Antonia Manduca, Patrizia Campolongo and Viviana Trezza
Rev. Neurosci. 2012; 23(5-6): 707–722
DOI 10.1515/revneuro-2012-0074
Mother-infant interactions are essential for proper neurobehavioral development of the offspring, and disruptions in those relationships may result in neuroendocrine, neurochemical and behavioral alterations at adulthood. The neural circuitries involved in mother-infant interactions have not been completely elucidated yet. The brain endocannabinoid system plays an essential role in prenatal and postnatal neurobehavioral development. Here, we will summarize and discuss the available findings about the role of endocannabinoids in three key aspects of mother-infant interactions in rodents: suckling, maternal behavior and separationinduced ultrasonic vocalizations (USVs). The studies reviewed here show that endocannabinoids are not only involved in suckling initiation and, therefore, in the feeding and growth of the offspring, but also regulate the emotional reactivity of rodent pups, as measured by the rate of isolation-induced USVs. Conversely, less information is available about endocannabinoid modulation of maternal behavior, and therefore more research in this direction is warranted. Indeed, since Cannabis sativa preparations are widely used by young people, including pregnant and lactating women, it is important to understand whether developmental exposure to cannabinoids interferes with mother-infant bond formation, potentially leading to neurodevelopmental alterations and increased vulnerability to psychopathology later in life.
Cannabinoids and cancer: causation, remediation, and palliation
Wayne Hall, MacDonald Christie, David Currow
Lancet Vol 6 January, 2005
http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.841.5709&rep=rep1&type=pdf
This review discusses three different associations between cannabinoids and cancer. First, it assesses evidence that smoking of cannabis preparations may cause cancers of the aerodigestive and respiratory system. There have been case reports of upper-respiratory-tract cancers in young adults who smoke cannabis, but evidence from a few epidemiological cohort studies and case-control studies is inconsistent. Second, there is mixed evidence on the effects of THC and other cannabinoids on cancers: in some in vitro and in vivo studies THC and some synthetic cannabinoids have had antineoplastic effects, but in other studies THC seems to impair the immune response to cancer. As yet there is no evidence that THC or other cannabinoids have anticancer effects in humans. Third, 9 -tetrahydrocannabinol (THC) may treat the symptoms and side-effects of cancer, and there is evidence that it and other cannabinoids may be useful adjuvant treatments that improve appetite, reduce nausea and vomiting, and alleviate moderate neuropathic pain in patients with cancer. The main challenge for the medical use of cannabinoids is the development of safe and effective methods of use that lead to therapeutic effects but that avoid adverse psychoactive effects. Furthermore, medical, legal, and regulatory obstacles hinder the smoking of cannabis for medical purposes. These very different uses of cannabinoids are in danger of being confused in public debate, especially in the USA where some advocates for the medical use of cannabinoids have argued for smoked cannabis rather than pharmaceutical cannabinoids. We review the available evidence on these three issues and consider their implications for policy. .
Cannabis and the developing brain: Insights from behavior
Viviana Trezza, Vincenzo Cuomo, Louk J.M.J. Vanderschuren
European Journal of Pharmacology 585 (2008) 441-452
DOI: 10.1016/j.ejphar.2008.01.058
The isolation and identification, in 1964, of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, opened the door to a whole new field of medical research. The exploration of the therapeutic potential of THC and other natural and synthetic cannabinoid compounds was paralleled by the discovery of the endocannabinoid system, comprising cannabinoid receptors and their endogenous ligands, which offered exciting new insights into brain function. Besides its well-known involvement in specific brain functions, such as control of movement, memory and emotions, the endocannabinoid system plays an important role in fundamental developmental processes such as cell proliferation, migration and differentiation. For this reason, changes in its activity during stages of high neuronal plasticity, such as the perinatal and the adolescent period, can have long-lasting neurobehavioral consequences. Here, we summarize human and animal studies examining the behavioral and neurobiological effects of in utero and adolescent exposure to cannabis. Since cannabis preparations are widely used and abused by young people, including pregnant women, understanding how cannabinoid compounds affect the developing brain, leading to neurobehavioral alterations or neuropsychiatric disorders later in life, is a serious health issue. In addition, since the endocannabinoid system is emerging as a novel therapeutic target for the treatment of several neuropsychiatric diseases, a detailed investigation of possible adverse effects of cannabinoid compounds on the central nervous system (CNS) of immature individuals is warranted .
Cannabis suppresses antitumor immunity by inhibiting JAK/ STAT signaling in T cells through CNR2
Xinxin Xiong, Siyu Che, Jianfei She, Hua You, Han Yan, Chao Yan, Ziqian Fan, Jianeng Zhan, Xiuyu Ca, Xingjun Don, Tiebang Kan, Wende Li and Penghui Zhou
Signal Transduction and Targeted Therapy
DOI: 10.1038/s41392-022-00918-y
https://www.nature.com/articles/s41392-022-00918-y.pdf
The combination of immune checkpoint blockade (ICB) with chemotherapy significantly improves clinical benefit of cancer treatment. Since chemotherapy is often associated with adverse events, concomitant treatment with drugs managing side effects of chemotherapy is frequently used in the combination therapy. However, whether these ancillary drugs could impede immunotherapy remains unknown. Here, we showed that Δ 9-tetrahydrocannabinol (THC), the key ingredient of drugs approved for the treatment of chemotherapy-caused nausea, reduced the therapeutic effect of PD-1 blockade. The endogenous cannabinoid anandamide (AEA) also impeded antitumor immunity, indicating an immunosuppressive role of the endogenous cannabinoid system (ECS). Consistently, high levels of AEA in the sera were associated with poor overall survival in cancer patients. We further found that cannabinoids impaired the function of tumor-specific T cells through CNR2. Using a knock-in mouse model expressing a FLAG-tagged Cnr2 gene, we discovered that CNR2 binds to JAK1 and inhibits the downstream STAT signaling in T cells. Taken together, our results unveiled a novel mechanism of the ECS-mediated suppression on T-cell immunity against cancer, and suggest that cannabis and cannabinoid drugs should be avoided during immunotherapy.
Delta‑9‑tetrahydrocannabinol reduces willingness to exert effort in women
Margaret C. Wardle · Elisa Pabon · Heather E. Webber · Harriet de Wit
Psychopharmacology
DOI: 10.1007/s00213-021-06032-1
https://link.springer.com/content/pdf/10.1007/s00213-021-06032-1.pdf
Background The use of cannabis has been clinically associated with decreased motivation to engage in normally rewarding activities. However, evidence from previous controlled studies is mixed. Method In this study, we examined the effects of acute delta-9-tetrahydrocannabinol (THC) versus placebo on a task measuring willingness to exert effort for rewards. This is a secondary analysis of a larger study examining interactions between ovarian hormones and THC. In this within-subjects study, oral THC and placebo were administered under double-blind conditions in counterbalanced order to healthy young adult (M age=24 years) women with previous cannabis experience who were not regular users. Forty subjects completed three 4-h sessions with PL, 7.5 and 15 mg THC, while an additional 18 completed only PL and 15 mg THC sessions (design abridged due to pandemic). At each session, they completed a task consisting of making repeated choices between a hard and an easy task, which were worth varying amounts of money at varying probabilities. Results THC dose-dependently decreased hard task choices (drug effect, b= −0.79, SE=0.29, z= −2.67, p<0.01), especially at moderate to high expected values of reward (drug×probability×amount interaction, b=0.77, SE=0.38, z=1.99, p=0.04). THC also slowed task performance (drug efect, b=0.01, SE=0.005, t(5.24)=2.11, p=0.04), but the effect of THC on choice was still significant after controlling for this psychomotor slowing. Conclusions These fndings support the idea that cannabis acutely reduces motivation to earn non-drug rewards. Still to be determined are the neurochemical mechanisms underlying this efect.
Development of intestinal bioavailability orediction (IBP) and phytochemical relative antitoxidant potential prediction (PRAPP) models for optimizing functional food value of Cannabis sativa (hemp).
Kimber Wise, Sophie N.B. Selby-Pham, Jamie Selby-Pham and Harsharn Gill
INTERNATIONAL JOURNAL OF FOOD PROPERTIES
2020, VOL. 23, NO. 1, 1287–1295
DOI: 10.1080/10942912.2020.1797783
Oxidative stress and inflammation (OSI) occurs naturally during many biological processes including digestion, metabolism, and exercise. While small, transient amounts of OSI are considered normal, unregulated, or chronic OSI can damage the vascular-circulatory system, which can result in chronic illnesses such as cardiovascular disease (CVD), atherosclerosis, and cancer. Antioxidant phytochemicals have the capacity to mitigate OSI through radical scavenging activity or the induction of endogenous mechanisms, but to achieve optimal reductions in OSI, the timing of antioxidant effects must occur during the onset of OSI – a concept known as ‘bio-matching.’ Additionally, the bioavailability and antioxidant capacity of active phytochemicals should be accounted for during pharmacokinetic assessments to guide bio-matching. Herein two quantitative structure–activity relationship (QSAR) predictive models are presented: the intestinal absorption prediction (IBP) model for predicting compound bioavailability (r2 = 0.93), and the phytochemical relative antioxidant potential prediction (PRAPP) model for predicting antioxidant capacity (r2 = 0.89). Application of these models to a characterized hemp meal phytochemical profile, along with established models for predicting Tmax and Tó, generated a composite antioxidant fingerprint, which predicted a peak in antioxidant activity 36 min after ingestion in liquid form. Accordingly, hemp meal-based protein powders (a common exercise supplement) should be consumed 26 min prior to completion of exercise to achieve bio-matching with the onset of exercise-induced OSI 10 min after exercise. The IBP and PRAPP models presented herein could be useful tools in understanding phytochemical complex antioxidant pharmacodynamics and in optimizing the consumption of hemp meal and other functional foods to achieve bio-matching of composite antioxidant activity with OSI profiles. .
IC Medical Cannabis/Endocannabinoids Pt 2 E-Z 15 .
Endocannabinoid System: An overview of its potential in current medical practice
Zadalla Mouslech, Vasiliki Valla
Neuro Endocrinology Letters 30(2):153-179 February 2009 https://www.researchgate.net/public...cal_practice_Neuro_Endocrinol_Lett_30_153-179 The endocannabinoid system (ECS) is a lipid signalling system, comprising of the endogenous cannabis-like ligands (endocannabinoids) anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which derive from arachidonic acid. These bind to a family of G-protein-coupled receptors, called CB1 and CB2. The cannabinoid receptor 1 (CB1R) is distributed in brain areas associated with motor control, emotional responses, motivated behaviour and energy homeostasis. In the periphery, the same receptor is expressed in the adipose tissue, pancreas, liver, GI tract, skeletal muscles, heart and the reproduction system. The CB2R is mainly expressed in the immune system regulating its functions. Endo cannabinoids are synthesized and released upon demand in a receptor-dependent way. They act as retrograde signalling messengers in GABAergic and glutamatergic synapses and as modulators of postsynaptic transmission, interacting with other neurotransmitters. Endocannabinoids are transported into cells by a specific uptake system and degraded by the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). The ECS is involved in various pathophysiological conditions in central and peripheral tissues. It is implicated in the hormonal regulation of food intake, cardiovascular, gastrointestinal, immune, behavioral, antiproliferative and mammalian reproduction functions. Recent advances have correlated the ECS with drug addiction and alcoholism. The growing number of preclinical and clinical data on ECS modulators is bound to result in novel therapeutic approaches for a number of diseases currently treated inadequately. The ECS dysregulation has been correlated to obesity and metabolic syndrome pathogenesis. Rimonabant is the first CB1 blocker launched to treat cardiometabolic risk factors in obese and overweight patients. Phase III clinical trials showed the drug's ability to regulate intra-abdominal fat tissue levels, lipidemic, glycemic and inflammatory parameters. However, safety conerns have led to its withdrawal. The role of endocannabinoids in mammalian reproduction is an emerging research area given their implication in fertilization, preimplantation embryo and spermatogenesis. The relevant preclinical data on endocannabinoid signalling open up new perspectives as a target to improve infertility and reproductive health in humans. .
Inhalation Absorption Prediction (IAP) Model for Predicting Medicinal Cannabis Phytochemical Pharmacokinetics
Kimber Wise, Harsharn Gill, Jamie Selby-Pham
Pharmacogn. Commn. 2019; 9(3): 85-90
https://phcogcommn.org/wp-content/uploads/2021/08/PharmaComm-9-3-85.pdf
Introduction: The medicinal benefits from inhalation of Cannabis sativa phytochemicals have been extensively reported. Whilst in-silico models are available for prediction of phytochemical pharmacokinetics post-ingestion, no models are available to accurately predict inhalation pharmacokinetics. Therefore, the aim of this study was to explore the relationship between phytochemical physicochemical properties and inhalation pharmacokinetics and to develop an in-silico model for predicting the time of maximal compound concentration in plasma (Tmax) and compound elimination half-life (T.), following inhalation. Methods: A training set of compound pharmacokinetic data was collated from previous publications and compared to physicochemical parameters using regression analyses. Physicochemical parameters that correlated with Tmax and T. were combined to develop a statistical model, which constructs functional fingerprints predicting compound concentrations in plasma post inhalation. Predicted functional fingerprints for three cannabis bioactive compounds were constructed and biomatched against previously reported physiological effects. Results: Inhalation Tmax was predicted (r2 = 0.84) by compound volume (Vol), topological surface area (TPSA) and molecular weight (MW), whilst T. was predicted (r2 = 0.87) by molecular weight, volume and number of rotatable bonds (nrot). The resulting inhalation absorption prediction (IAP) model was achieved by combining Tmax and T. predictions. The IAP model was applied to cannabis metabolites which accurately predicted decay functions in-vivo and biomatching with associated physiological effects. Conclusion: The IAP model was applied successfully to cannabis phytochemicals to explore the pharmacokinetics underpinning their medicinal effects. This study demonstrates the utility of the IAP model and highlights its applicability during the investigation of medicinal plants and their modes of action. .
Investigation of hand functions in individuals with cannabis and its derivatives use disorder
Bekir Güçlü, Baki Umut Tuğay, Fatih Özden, Esra Erğun Keşli & Cemal Onur Noyan
Irish Journal of Medical Science (1971 -) (2022)https://link.springer.com/article/10.1007/s11845-022-03006-w
Background
The present study was aimed to compare the grip/pinch strengths and manual dexterity of individuals with and without the use of cannabis and its derivatives.Methods
A cross-sectional prospective study was conducted with 66 individuals, including 33 cases with the use of cannabis (and its derivatives) and 33 age- and sex-matched controls. Grip and pinch strengths were evaluated with a dynamometer. The Nine-Hole Peg Test (9HPT), Minnesota Manual Dexterity Test (MMDT), and Michigan Hand Outcomes Questionnaire (MHQ) were used to assess the hand function.Results
The hand grip strength and dominant hand 2-point pinch (2PP) grip strength were less in individuals with substance use disorder (SUD) (p < 0.05). The 9HPT duration of the SUD patients was higher (p < 0.05). On the other hand, the MMDT insertion and rotation test results were different between the groups (p < 0.05). Grip strength was related with the MMDT insertion and rotation tests (r = −0.411 to −0.480). There was significant correlation between grip strength with dominant hand 9HPT (r = −0.370) and between dominant hand 3-point pinch (3PP) strength with MMDT insertion (r = −0.378). In addition, dominant hand 2PP strength was correlated with overall hand function of MHQ (r = 0.382).Conclusion
The individuals with cannabis use disorder showed reduced grip strength on both sides and decreased 2PP strength on the dominant side compared to healthy individuals. In addition, there is a decrease in the hand skills of individuals with cannabis use disorder. Decreased grip strength of individuals with cannabis use disorder affected their hand skills negatively.Find PDF
Marijuana Dependence: Not Just Smoke and Mirrors
Divya Ramesh, Joel E. Schlosburg, Jason M. Wiebelhaus, Aron H. Lichtman
ILAR J. 2011 January ; 52(3): 295–308. doi:10.1093/ilar.52.3.295
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606907/pdf/nihms380778.pdf
Marijuana (Cannabis sativa) is the most commonly used illicit drug worldwide as well as in the Unites States. Prolonged use of marijuana or repeated administration of its primary psychoactive constituent, Δ9 -tetrahydrocannabinol (THC), can lead to physical dependence in humans and laboratory animals. The changes that occur with repeated cannabis use include alterations in behavioral, physiological, and biochemical responses. A variety of withdrawal responses occur in cannabis-dependent individuals: anger, aggression, irritability, anxiety and nervousness, decreased appetite or weight loss, restlessness, and sleep difficulties with strange dreams. But the long halflife and other pharmacokinetic properties of THC result in delayed expression of withdrawal symptoms, and because of the lack of contiguity between drug cessation and withdrawal responses the latter are not readily recognized as a clinically relevant syndrome. Over the past 30 years, a substantial body of clinical and laboratory animal research has emerged supporting the assertion that chronic exposure to cannabinoids produces physical dependence and may contribute to drug maintenance in cannabis-dependent individuals. However, no medications are approved to treat cannabis dependence and withdrawal. In this review, we describe preclinical and clinical research that supports the existence of a cannabinoid withdrawal syndrome. In addition, we review research evaluating potential pharmacotherapies (e.g., THC, a variety of antidepressant drugs, and lithium) to reduce cannabis withdrawal responses and examine how expanded knowledge about the regulatory mechanisms in the endocannabinoid system may lead to promising new therapeutic targets. .
Medicinal cannabis pilot programme (Denmark)
https://laegemiddelstyrelsen.dk/en/special/medicinal-cannabis-/medicinal-cannabis-pilot-programme/
On 1 January 2018, a medicinal cannabis pilot programme entered into force. The programme allows doctors to prescribe new types of cannabis products that were not legal in Denmark before. The pilot programme runs until 31 December 2025.
The purpose of the pilot programme is to offer patients a lawful way of testing treatment with medicinal cannabis if they have experienced no benefits from authorised medicines. That is the intention with the programme.
The products available in the pilot programme depend on the manufacturers of cannabis products. They apply for admission of cannabis products to the programme with the aim of making these products available for prescribers. The available cannabis products are therefore likely to change during the course of the pilot programme.
The currently available cannabis products can be seen on Medicine Prices, www.medicinpriser.dk.
The cannabis products included in the pilot programme are not authorised medicines – not in Denmark or any other country. Usually, the products are not tested in clinical trials like authorised medicines. So compared to authorised medicines, doctors have limited evidence of the effects and side effects. One of the implications thereof is that doctors must accept full responsibility for the prescription of a product, e.g. by determining the dose for the individual patient. They can neither consult a package leaflet nor a summary of product characteristics to assess what beneficial effects or side effects the individual patient is likely to expect
Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders
Alline Cristina Campos, Fabricio Arau´jo Moreira, Felipe Villela Gomes, Elaine Aparecida Del Bel and Francisco Silveira Guimara˜es
Phil. Trans. R. Soc. B (2012) 367, 3364–3378
doi:10.1098/rstb.2011.0389
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481531/pdf/rstb20110389.pdf
Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound D9 -tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1Amediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamidemediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARg receptors agonism, intracellular (Ca2þ) increase, etc.), on CBD behavioural effects. .
Neural responses to reward anticipation and feedback in adult and adolescent cannabis users and controls
Martine Skumlien, Claire Mokrysz, Tom P. Freeman, Matthew B. Wall, Michael Bloomfield, Rachel Lees, Anna Borissova, Kat Petrilli, James Carson, Tiernan Coughlan, Shelan Ofori, Christelle Langley, Barbara J. Sahakian , H. Valerie Curran and Will Lawn
Neuropsychopharmacology Nature
https://www.nature.com/articles/s41386-022-01316-2.pdf .
Chronic use of drugs may alter the brain’s reward system, though the extant literature concerning long-term cannabis use and neural correlates of reward processing has shown mixed results. Adolescents may be more vulnerable to the adverse effects of cannabis than adults; however, this has not been investigated for reward processing. As part of the ‘CannTeen’ study, in the largest functional magnetic resonance imaging study of reward processing and cannabis use to date, we investigated reward anticipation and feedback in 125 adult (26–29 years) and adolescent (16–17 years) cannabis users (1–7 days/week cannabis use) and genderand age-matched controls, using the Monetary Incentive Delay task. Blood-oxygen-level-dependent responses were examined using region of interest (ROI) analyses in the bilateral ventral striatum for reward anticipation and right ventral striatum and left ventromedial prefrontal cortex for feedback, and exploratory whole-brain analyses. Results showed no User-Group or User-Group × Age-Group effects during reward anticipation or feedback in pre-defined ROIs. These null findings were supported by post hoc Bayesian analyses. However, in the whole-brain analysis, cannabis users had greater feedback activity in the prefrontal and inferior parietal cortex compared to controls. In conclusion, cannabis users and controls had similar neural responses during reward anticipation and in hypothesised reward-related regions during reward feedback. The whole-brain analysis revealed tentative evidence of greater fronto-parietal activity in cannabis users during feedback. Adolescents showed no increased vulnerability compared with adults. Overall, reward anticipation and feedback processing appear spared in adolescent and adult cannabis users, but future longitudinal studies are needed to corroborate this.
Neuroprotective Effects of Phytocannabinoid-Based Medicines in Experimental Models of Huntington’s Disease
Onintza Sagredo, M. Ruth Pazos, Valentina Satta, Jose ́ A. Ramos, Roger G. Pertwee, and Javier Ferna ́ndez-Ruiz
Journal of Neuroscience Research 89:1509–1518 (2011)
DOI: 10.1002/jnr.22682
We studied whether combinations of botanical extracts enriched in either D9-tetrahydrocannabinol (D9-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, provide neuroprotec- tion in rat models of Huntington’s disease (HD). We used rats intoxicated with 3-nitropropionate (3NP) that were given combinations of D9-THC- and CBD-enriched bo- tanical extracts. The issue was also studied in malonate- lesioned rats. The administration of D9-THC- and CBD- enriched botanical extracts combined in a ratio of 1:1 as in Sativex attenuated 3NP-induced GABA deficiency, loss of Nissl-stained neurons, down-regulation of Crecep- tor and IGF-1 expression, and up-regulation of calpain expression, whereas it completely reversed the reduction in superoxide dismutase-1 expression. Similar responses were generally found with other combinations of D9-THC- and CBD-enriched botanical extracts, suggesting that these effects are probably related to the antioxidant and CB and CB receptor-independent properties of both phytocannabinoids. In fact, selective antagonists for both receptor types, i.e., SR141716 and AM630, respectively, were unable to prevent the positive effects on calpain expression caused in 3NP-intoxicated rats by the 1:1 combination of D9-THC and CBD. Finally, this combina- tion also reversed the up-regulation of proinflammatory markers such as inducible nitric oxide synthase observed in malonate-lesioned rats. In conclusion, this study provides preclinical evidence in support of a beneficial effect of the cannabis-based medicine Sativex as a neuroprotective agent capable of delaying disease pro- gression in HD, a disorder that is currently poorly man- aged in the clinic, prompting an urgent need for clinical trials with agents showing positive results in preclinical studies.
Sex differences in the acute effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC)
Psychopharmacology April 2022 DOI: 10.1007/s00213-022-06135-3
Anahita Bassir Nia, Maria J. Orejarena, Leigh Flynn, Christina Luddy, Deepak Cyril D’Souza, Patrick D. Skosnik, Brian Pittman, Mohini Ranganathan
https://www.researchgate.net/public...travenous_IV_delta-9_tetrahydrocannabinol_THC
Background Cannabis is the most common illicit drug used in the USA and its use has been rising over the past decade, while the historical gap in rates of use between men and women has been decreasing. Sex differences in the effects of cannabinoids have been reported in animal models, but human studies are sparse and inconsistent. We investigated the sex differences in the acute subjective, psychotomimetic, cognitive, and physiological effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis. Methods Healthy male and female individuals, with limited exposure to cannabis, participated in a double blind, placebo-controlled study of intravenous (IV) placebo or THC at two doses (0.015 mg/kg and 0.03 mg/kg). Visual analog scale (VAS) was used to measure subjective effects, Psychotomimetic States Inventory (PSI) and the Clinician-Administered Dissociative Symptoms Scale (CADSS) were used to assess the psychotomimetic effects and perceptual alterations, respectively, and Rey Auditory Verbal Learning Task (RAVLT) was used to evaluate cognitive effects. Outcome variables were represented as the peak change from baseline for each variable, except RAVLT which was used only once per the test day after the subjective effects. Results A total of 42 individuals participated in this study. There were no significant differences between male and female participants in background characteristics. There was a significant main effect of sex on the VAS scores for THC-induced “High” (F1,38 = 4.27, p < 0.05) and a significant dose × sex interaction (F2,77 = 3.38, p < 0.05) with female participants having greater “High” scores than male participants at the lower THC dose (0.015 mg/kg). No other sex differences were observed in acute subjective, psychotomimetic, cognitive, or physiological effects of THC. Conclusion There were significant sex differences in subjective effects of feeling “High” at a lower dose of THC. However, there were no other sex-related differences in the subjective, physiological, or cognitive effects of THC.
Find PDF
Standardized Cannabis Smoke Extract Induces Inflammation in Human Lung Fibroblasts
Front. Pharmacol., 28 March 2022 https://doi.org/10.3389/fphar.2022.852029https://www.frontiersin.org/articles/10.3389/fphar.2022.852029/full?xnpe_tifc=4.V8OIV7h.VD4dYXb.nJxypZhfEWVjQsVuU_O.VjOIolhkUstIYDhIbA4FP_hNl8bdhNtIHpbDPNxfb7bDHdb9p_4fe.bubXxFzZxFVpbdnD&utm_source=eNews&utm_campaign=TCS Newsletter Week 16 2022&utm_medium=email
The Endocannabinoid System in Huntington’s Disease
M.R. Pazos, O. Sagredo and J. Fernández-Ruiz
Current Pharmaceutical Design, 2008, 14, 2317-2325
DOI:10.2174/138161208785740108
The hypokinetic profile of certain cannabinoid agonists becomes these compounds as promising medicines to attenuate the hyperkinesia that characterizes the first grades of Huntington’s disease (HD) and that represents the major neurological abnormality in this disease. The fact that CB1 receptors, the receptor type involved in motor effects of cannabinoid agonists, are significantly reduced in the basal ganglia during the progression of HD represents a convincing explanation for the hyperkinesia typical of this disorder and supports the usefulness of enhancing CB1 receptor signaling in HD. However, further studies revealed that the key property that enables certain cannabinoid agonists to reduce hyperkinesia is their capability to directly activate vanilloid TRPV1 receptors. Cannabinoids may also serve to delay/arrest the progression of HD by protecting striatal projection neurons from death. Several cannabinoid agonists have been tested for this purpose in various animal models of HD, and these studies revealed that the major characteristics that enable cannabinoids to provide neuroprotection are three: (i) a reduction in inflammatory events exerted through activating CB2 receptors located in glial cells; (ii) a normalization of glutamate homeostasis, then limiting excitotoxicity, an effect that would be exerted through CB1 receptors; and (iii) an antioxidant effect exerted by cannabinoid receptor-independent mechanisms. The changes experienced by the endocannabinoid signaling system during the striatal degeneration support this neuroprotective effect, particularly the up-regulatory responses proved by CB2 receptors in glial cells recruited at lesioned sites. The present article will review the neurochemical and pharmacological bases that sustain the importance of the endocannabinoid system in the pathophysiology of HD, trying to collect the present information and the future lines for research on the therapeutic potential of this system in this disorder.
The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract
Federico Massa . Martin Storr . Beat Lutz
J Mol Med (2005) 83: 944–954
DOI 10.1007/s00109-005-0698-5
Numerous investigations have recently demonstrated the important roles of the endocannabinoid system in the gastrointestinal (GI) tract under physiological and pathophysiological conditions. In the GI tract, cannabinoid type 1 (CB1) receptors are present in neurons of the enteric nervous system and in sensory terminals of vagal and spinal neurons, while cannabinoid type 2 receptors are located in immune cells. Activation of CB1 receptors was shown to modulate several functions in the GI tract, including gastric secretion, gastric emptying and intestinal motility. Under pathophysiological conditions induced experimentally in rodents, the endocannabinoid system conveys protection to the GI tract (e.g. from inflammation and abnormally high gastric and enteric secretions). Such protective activities are largely in agreement with anecdotal reports from folk medicine on the use of Cannabis sativa extracts by subjects suffering from various GI disorders. Thus, the endocannabinoid system may serve as a potentially promising therapeutic target against different GI disorders, including frankly inflammatory bowel diseases (e.g. Crohn’s disease), functional bowel diseases (e.g. irritable bowel syndrome) and secretion- and motilityrelated disorders. As stimulation of this modulatory system by CB1 receptor agonists can lead to unwanted psychotropic side effects, an alternative and promising avenue for therapeutic applications resides in the treatment with CB1 receptor agonists that are unable to cross the blood–brain barrier, or with compounds that inhibit the degradation of endogenous ligands (endocannabinoids) of CB1 receptors, hence prolonging the activity of the endocannabinoid system.
The Medical Geography of Cannabinoid Botanicals in Washington State: Access, Delivery, and Distress
Sunil Kumar Aggarwal
University of Washington 2008
http://www.cannabinologist.org/Documents/SunilAggarwal_Dissertation.pdf
Though rendered dormant by a post-1937 Cannabis sativa L. prohibition, the emerging field of cannabinoid medicine is growing in the United States as ever greater numbers of physicians become educated about the physiologic importance of the endogenous cannabinoid system and about the wide safety margins and broad clinical efficacies of cannabinoid drugs, available in both purely botanical and purely chemical varieties and useful for managing pain and other conditions in the growing chronically and critically ill patient population. Research presented here is focused on medical access and delivery of cannabinoid botanicals in Washington State and seeks to map the geography of this developing cannabinoid medical care system by taking medical geographic “snapshots” of two purposefully chosen locations: a rural clinic site in Washington State where patients currently access cannabinoid botanicals for medical use in the treatment of chronic pain syndromes with acceptable safety under medical supervision and another site where qualifying patients are delivered environmentallyculled cannabinoid botanicals. At the former site, retrospective chart reviews were conducted with 139 patients with chronic pain, and at the latter site, a convenience sample of 37 qualifying patients delivered a monoclonal lot of cannabinoid botanical medicine were prospectively studied using standard and tailored survey instruments. A political ecology of disease approach was employed to rationalize and depathologize patients’ mental distress at potentially facing possession-related legal problems due to their consumption of the still-contraband biota. Results provide quantitative and qualitative insight into the frail health status in both samples of qualifying patients and give a grounded understanding of the lengths that patients and care providers go, despite multiple hurdles, to access and deliver treatment with cannabinoid botanicals that relieves patients’ diverse symptoms and improves their health-related quality-of life. .
The Medicalization of Cannabis
Edited by S M Crowther, L A Reynolds and E M Tansey
The transcript of a Witness Seminar held by the Wellcome Trust Centre for the History of Medicine at UCL, London, on 24 March 2009
https://qmro.qmul.ac.uk/xmlui/bitst...icalizationofCannabis2010FINAL.pdf?sequence=2
CONTENTS Illustrations and credits v
Abbreviations vii
Witness Seminars: Meetings and publications; Acknowledgements E M Tansey, L A Reynolds and S M Crowther ix
Introduction Leslie Iversen xix
Transcript Edited by S M Crowther, L A Reynolds and E M Tansey 1
Appendix 1 Diagrams of the structures of some major plant cannabinoids and of certain structurally related synthetic cannabinoids 73
References 75
Biographical notes 89
Index 97
The medical use of cannabis has a very long history; it was used for thousands of years in Indian and other Asian medicine and was first introduced to the west in the mid-nineteenth century by a brilliant young doctor, W B O’Shaughnessy, returning to England after service in India. Cannabis was taken up enthusiastically by physicians in Europe and the US and was widely used for almost a hundred years until it fell out of favour as new and more easily standardized medicines became available and government regulations were imposed. Tincture of cannabis finally left the British Pharmacopoeia in the mid-1970s.
This Witness Seminar, however, was focused not on this early history but on the resurgence of interest in medical cannabis that has occurred in the past few decades. It brought together a group of people with diverse expertise who had witnessed at first hand the development of this field. Although the seminar did not deal at all with the recreational use of cannabis, it is impossible to consider the history of medical cannabis without considering the impact that the rapid growth of the illicit recreational use of the drug in the latter part of the twentieth century has had. The ‘cannabis wars’ have been fought between those who believe it to be harmless and medically useful, and those who see it as a danger to health and to society without any legitimate medical use. For many years the stigmatization of cannabis had a negative influence on the availability of research funding and promoted reluctance on the part of doctors and pharmaceutical companies to be involved in research on the medical uses of cannabis.
Topical Cannabidiol (CBD) After Total Knee Arthroplasty Does Not Decrease Pain or Opioid Use: A Prospective Randomized Double-Blinded Placebo-Controlled Trial
Amer Haffar, Irfan A Khan, Mohammad S Abdelaal, Samik Banerjee, Peter F SharkeyJ Arthroplasty April 2022 doi: 10.1016/j.arth.2022.03.081
https://pubmed.ncbi.nlm.nih.gov/35390457/
https://www.arthroplastyjournal.org/article/S0883-5403(22)00383-7/fulltextBackground: Multimodal analgesia has become the standard of care for pain management following total knee arthroplasty (TKA). Cannabidiol (CBD) is increasingly utilized in the postoperative period. The purpose of this study was to analyze the analgesic benefits of topical CBD following primary TKA.
Methods: In this randomized double-blinded placebo-controlled trial, 80 patients undergoing primary unilateral TKA applied topical CBD (CBD; n=19), essential oil (EO; n=21), CBD and essential oil (CBD+EO; n=21), or placebo (PLA; n=19) thrice daily around the knee for two weeks postoperatively. This supplemented a standardized multimodal analgesic protocol. Outcomes included visual analog scale (VAS) pain and numeric rating scale (NRS) sleep scores (collected on postoperative day [POD] 0, 1, 2, 7, 14, 42), and cumulative postoperative opioid use (42 days).
Results: Demographic characteristics were similar among the four cohorts. Preoperative VAS and NRS scores were similar among groups. The CBD cohort had a higher mean VAS pain score on POD 2 compared to the EO cohort (CBD: 69.9 ± 19.3 vs. EO: 51.0 ± 18.2; p=0.013). No significant differences existed for VAS scores at other times, and no significant differences were observed for postoperative NRS sleep scores or postoperative opioid use at any time point.
Conclusions: Utilization of topical CBD in supplement to multimodal analgesia did not reduce pain or opioid consumption, or improve sleep scores following TKA. These results suggest the local effects of topical CBD are not beneficial for providing additional pain relief after TKA.
Find PDF
Last edited:
