Cannabis use may attenuate neurocognitive performance deficits resulting from methamphetamine use disorder

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“Objective: Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders.

Method: 423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M-/M+) and/or cannabis (C-/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition.

Results: Globally, M+C+ performed worse than M-C- but better than M+C-. M+C+ outperformed M+C- on measures of verbal fluency, information processing speed, learning, memory, and working memory. M-C+ did not display lower performance than M-C- globally or on any domain measures, and M-C+ even performed better than M-C- on measures of learning, memory, and working memory.

Conclusions: Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.”

https://pubmed.ncbi.nlm.nih.gov/37553288/

https://www.cambridge.org/core/journals/journal-of-the-international-neuropsychological-society/article/abs/cannabis-use-may-attenuate-neurocognitive-performance-deficits-resulting-from-methamphetamine-use-disorder/8AC3E796BDBD8E387D685EB892C63244

Cannabis use for exercise recovery in trained individuals: a survey study

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“Background: Cannabis use, be it either cannabidiol (CBD) use and/or delta-9-tetrahydrocannabinol (THC) use, shows promise to enhance exercise recovery. The present study aimed to determine if individuals are using CBD and/or THC as a means of recovery from aerobic and/or resistance exercise, as well as additional modalities that might be used to aid in recovery.

Methods: Following consent, 111 participants (Mean ± SD: Age: 31 ± 13 years) completed an anonymous survey. All participants were regularly using cannabis (CBD and/or THC) as well as were currently exercising. Questions pertained to level of cannabis use, methods used for consumption of cannabis, exercise habits, exercise recovery strategies, and demographics.

Results: Eighty-five percent of participants reported participating in aerobic training. In addition, 85% of participants also reported regular participation in resistance exercise. Seventy-two percent of participants participated in both aerobic and resistance exercise. Ninety-three percent of participants felt that CBD use assisted them with recovery from exercise, while 87% of participants felt the same regarding THC use.

Conclusions: Individuals who habitually use cannabis, CBD or THC, and regularly engage in exercise do feel that cannabis assists them with exercise recovery. More data are necessary to understand the role of cannabis in exercise recovery as well as perceived ergogenic benefits of cannabis by individuals who both regularly participate in exercise and habitually use cannabis.”

https://pubmed.ncbi.nlm.nih.gov/37542349/

“CBD or THC use have been suggested to play a role in pain management, inflammation, and sleep, which are hallmarks for recovery from exercise. While data are lacking, it is clear that individuals are using cannabis and believe cannabis to have a positive effect on recovery from exercise. The present study demonstrated that in addition to more traditional recovery methods, cannabis is used as an ergogenic recovery aid by individuals that exercise regularly.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-023-00198-5

Hippocampal differential expression underlying the neuroprotective effect of delta-9-tetrahydrocannabinol microdose on old mice

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“Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive compound of the cannabis plant and an exogenous ligand of the endocannabinoid system. In previous studies, we demonstrated that a single microdose of THC (0.002 mg/kg, 3-4 orders of magnitude lower than the standard dose for rodents) exerts distinct, long-term neuroprotection in model mice subjected to acute neurological insults. When administered to old, healthy mice, the THC microdose induced remarkable long-lasting (weeks) improvement in a wide range of cognitive functions, including significant morphological and biochemical brain alterations. To elucidate the mechanisms underlying these effects, we analyzed the gene expression of hippocampal samples from the model mice. Samples taken 5 days after THC treatment showed significant differential expression of genes associated with neurogenesis and brain development. In samples taken 5 weeks after treatment, the transcriptional signature was shifted to that of neuronal differentiation and survival. This study demonstrated the use of hippocampal transcriptome profiling in uncovering the molecular basis of the atypical, anti-aging effects of THC microdose treatment in old mice.”

https://pubmed.ncbi.nlm.nih.gov/37534036/

“Our findings imply that the THC microdose treatment alleviates age-dependent cognitive deficits by modulating multiple hallmarks of brain aging, supporting past hypotheses regarding the relation between aging and the endocannabinoid system.”

https://www.frontiersin.org/articles/10.3389/fnins.2023.1182932/full

Molecular pathway and structural mechanism of human oncochannel TRPV6 inhibition by the phytocannabinoid tetrahydrocannabivarin

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“The calcium-selective oncochannel TRPV6 is an important driver of cell proliferation in human cancers. Despite increasing interest of pharmacological research in developing synthetic inhibitors of TRPV6, natural compounds acting at this channel have been largely neglected. On the other hand, pharmacokinetics of natural small-molecule antagonists optimized by nature throughout evolution endows these compounds with a medicinal potential to serve as potent and safe next-generation anti-cancer drugs. Here we report the structure of human TRPV6 in complex with tetrahydrocannabivarin (THCV), a natural cannabinoid inhibitor extracted from Cannabis sativa. We use cryo-electron microscopy combined with electrophysiology, calcium imaging, mutagenesis, and molecular dynamics simulations to identify THCV binding sites in the portals that connect the membrane environment surrounding the protein to the central cavity of the channel pore and to characterize the allosteric mechanism of TRPV6 inhibition. We also propose the molecular pathway taken by THCV to reach its binding site. Our study provides a foundation for the development of new TRPV6-targeting drugs.”

https://pubmed.ncbi.nlm.nih.gov/37532722/

https://www.nature.com/articles/s41467-023-40362-2

Association between cannabis use and risk of diabetes mellitus type 2: A systematic review and meta-analysis

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“Background: Cannabis consumption exerts multiple effects on metabolism via various pathways, including glucose regulation and insulin secretion. Studies concerning the association between cannabis use and diabetes mellitus type 2 are discrepant.

Objective: This study was conducted to evaluate the association between cannabis use and type 2 diabetes mellitus (T2DM).

Search methods: We searched PubMed, Scopus, Embase, Proquest, Web of Science, and Cochrane Library with no time, language or study types restriction until July 1, 2022, using various forms of “cannabis” and “diabetes mellitus” search terms.

Selection criteria: Randomized control trials, cohort, and case-control studies investigating the relationship between cannabis consumption and diabetes mellitus type 2 were included.

Data collection and analysis: The Newcastle-Ottawa scale was used to assess the quality of studies. We pooled odds ratio (OR) with 95% confidence interval (CI) using the random-effects model, generic inverse variance method, DerSimonian and Laird approach.

Main results: A meta-analysis of seven studies, containing 11 surveys and 4 cohorts, revealed that the odds of developing T2DM in individuals exposed to cannabis was 0.48 times (95% CI: 0.39 to 0.59) lower than in those without cannabis exposure.

Conclusions: A protective effect of cannabis consumption on the odds of diabetes mellitus type 2 development has been suggested. Yet given the considerable interstudy heterogeneity, the upward trend of cannabis consumption and cannabis legalization is recommended to conduct studies with higher levels of evidence.”

https://pubmed.ncbi.nlm.nih.gov/37526051/

https://onlinelibrary.wiley.com/doi/10.1002/ptr.7973

The Exploration of Cannabis and Cannabinoid Therapies for Migraine

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“Purpose of review: There is increasing interest in the use of cannabis and cannabinoid therapies (CCT) by the general population and among people with headache disorders, which results in a need for healthcare professionals to be well versed with the efficacy and safety data. In this manuscript, we review cannabis and cannabinoid terminology, the endocannabinoid system and its role in the central nervous system (CNS), the data on efficacy, safety, tolerability, and potential pitfalls associated with use in people with migraine and headache disorders. We also propose possible mechanisms of action in headache disorders and debunk commonly held myths about its use.

Recent findings: Preliminary studies show that CCT have evidence for the management of migraine. While this evidence exists, further randomized, controlled studies are needed to better support its clinical use. CCT can be considered an integrative treatment added to mainstream medicine for people with migraine who are refractory to treatment and/or exhibit disability and/or interest in trying these therapies. Further studies are warranted to specify appropriate formulation, dosage, and indication(s). Although not included in guidelines or the AHS 2021 Consensus Statement on migraine therapies, with the legalization of CCT for medical or unrestricted use across the USA, recent systematic reviews highlighting the preliminary evidence for its use in migraine, it is vital for clinicians to be well versed in the efficacy, safety, and clinical considerations for their use. This review provides information which can help people with migraine and clinicians who care for them make mutual, well-informed decisions on the use of cannabis and cannabinoid therapies for migraine based on the existing data.”

https://pubmed.ncbi.nlm.nih.gov/37515745/

https://link.springer.com/article/10.1007/s11916-023-01144-z

Determining Antioxidant Activity of Cannabis Leaves Extracts from Different Varieties-Unveiling Nature’s Treasure Trove

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“Cannabis leaves contain a diverse range of antioxidants, including cannabinoids, flavonoids, and phenolic compounds, which offer significant health benefits. Utilising cannabis leaves as a source of antioxidants presents a cost-effective approach because they are typically discarded during the cultivation of cannabis plants for their seeds or fibres. Therefore, this presented study aimed to assess the antioxidant activity of the leaves of selected hemp cultivars, such as Białobrzeska, Tygra, and Henola, based on the results obtained with the 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid, ferric reducing antioxidant power, cupric reducing antioxidant capacity, and 2,2-Diphenyl-1-picrylhydrazyl assays. The cannabinoid profile was analysed for the antioxidant activity to the contents of cannabidiol (CBD), cannabigerol (CBG), Δ9-tetrahydrocannabinol (Δ9-THC), and cannabichromene (CBC), determined based on chromatographic assays. The following variables were tested: the impact of various extractants (methanol, ethanol, and isopropanol), and their mixtures (50:50, v/v, as well as extraction methods (maceration and ultra-sound-assisted extraction) significant in obtaining hemp extracts characterised by different cannabinoid profiles. The results revealed that the selection of extractant and extraction conditions significantly influenced the active compounds’ extraction efficiency and antioxidant activity. Among the tested conditions, ultrasound-assisted extraction using methanol yielded the highest cannabinoid profile: CBD = 184.51 ± 5.61; CBG = 6.10 ± 0.21; Δ9-THC = 0.51 ± 0.01; and CBC = 0.71 ± 0.01 μg/g antioxidant potential in Białobrzeska leaf extracts.”

https://pubmed.ncbi.nlm.nih.gov/37507928/

“Cannabis leaves are known to contain a wide range of antioxidants, and this also includes cannabinoids, which have been shown to have significant health benefits. Using cannabis leaves as an antioxidant source can be a cost-effective option as they are often discarded during the cultivation of cannabis plants for their seeds or fibres. Moreover, the use of cannabis leaves as a source of antioxidants may also have environmental benefits as it can reduce waste and promote sustainable agriculture practices. This current study illuminates that not only the flowers and seeds of cannabis possess potential health benefits, but also the leaves; moreover, a comprehensive understanding is fostered regarding the diverse therapeutic potential inherent in this plant. “

https://www.mdpi.com/2076-3921/12/7/1390

Cannabis use to manage opioid cravings among people who use unregulated opioids during a drug toxicity crisis

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“Background: Accumulating evidence has indicated that cannabis substitution is often used as a harm reduction strategy among people who use unregulated opioids (PWUO) and people living with chronic pain. We sought to investigate the association between cannabis use to manage opioid cravings and self-reported changes in opioid use among structurally marginalized PWUO.

Methods: The data were collected from a cross-sectional questionnaire administered to PWUO in Vancouver, Canada. Binary logistic regression was used to analyze the association between cannabis use to manage opioid cravings and self-reported changes in unregulated opioid use.

Results: A total of 205 people who use cannabis and opioids were enrolled in the present study from December 2019 to November 2021. Cannabis use to manage opioid cravings was reported by 118 (57.6%) participants. In the multivariable analysis, cannabis use to manage opioid cravings (adjusted Odds Ratio [aOR] = 2.13, 95% confidence interval [CI]: 1.07, 4.27) was significantly associated with self-reported reductions in opioid use. In the sub-analyses of pain, cannabis use to manage opioid cravings was only associated with self-assessed reductions in opioid use among people living with moderate to severe pain (aOR = 4.44, 95% CI: 1.52, 12.97). In the sub-analyses of males and females, cannabis use to manage opioid cravings was only associated with self-assessed reductions in opioid use among females (aOR = 8.19, 95% CI: 1.20, 55.81).

Conclusions: These findings indicate that cannabis use to manage opioid cravings is a prevalent motivation for cannabis use among PWUO and is associated with self-assessed reductions in opioid use during periods of cannabis use. Increasing the accessibility of cannabis products for therapeutic use may be a useful supplementary strategy to mitigate exposure to unregulated opioids and associated harm during the ongoing drug toxicity crisis.”

https://pubmed.ncbi.nlm.nih.gov/37481875/

https://www.sciencedirect.com/science/article/abs/pii/S0955395923001603?via%3Dihub

Offering an Alternative to Persons with Chronic Pain: How Access to Cannabis May Provide an Off-Ramp from Undesired Prescription Opioid Use

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“Background: Chronic pain (CP) is experienced by as many as 50 million Americans and can negatively impact physical and mental health. Prescribing opioids is the most common approach to address moderate to severe CP though these potent analgesics are associated with a significant number of side effects. One alternative some Americans are turning to for CP management is cannabis. In addition to serving as an alternative, many individuals with CP use cannabis in addition to using prescription opioids. This study examined individuals with CP who enrolled in the state of Illinois’ opioid diversion program, the Opioid Alternative Pilot Program (OAPP), which offers individuals aged 21 and older a separate pathway to access medical cannabis if they have or could receive a prescription for opioids as certified by a licensed physician.

Methods: Cross-sectional survey data were collected from 450 participants. We described participants and compared those who use only cannabis with those who use cannabis and opioids.

Results: While 16% of the respondents were cannabis-only users, 84% of the respondents were co-users of opioids and cannabis. Both groups considered opioid use risky (100% cannabis-only, 89% co-users,). The majority (73%) of respondents sought to completely stop or never start using opioids for CP. Cannabis-only users reported lower levels of pain compared to co-users. Co-users (85%) were more likely to have their routine provider as a cannabis certifying physician than cannabis-only users (69%).

Conclusion: With increasing clinical evidence, legalization and acceptance, researchers should continue to examine how cannabis may be a viable alternative to reduce the risk of prescription opioid side effects, misuse, or dependence. Our findings also inform health care providers and state policymakers who increasingly are being asked to consider how cannabis may reduce the potential for harmful outcomes among persons with CP who use prescription opioids.”

https://pubmed.ncbi.nlm.nih.gov/37484046/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/125

Perceived Effectiveness of Medical Cannabis Among Adults with Chronic Pain: Findings from Interview Data in a Three-Month Pilot Study

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“Objectives: Patient-reported outcomes are critical to evaluate the effectiveness of medical cannabis as an alternative treatment for chronic pain. This study examined the perceived effectiveness of medical cannabis for chronic pain management among middle-aged and older adults newly initiating medical cannabis.

Methods: Interview data from participants in a three-month pilot study were analyzed to assess the perceived effectiveness of medical cannabis on chronic pain and related outcomes. The interview was conducted after approximately one month of usage and responses were analyzed using the RADaR (Rigorous and Accelerated Data Reduction) technique.

Results: 51 adults initiating medical cannabis for chronic pain were interviewed (24 women, 27 men, mean age 54.4, SD = 12.0), with the majority (n=41) identifying as Non-Hispanic White followed by Non-Hispanic Black (n=7), Multi-racial (2), Hispanic White (1). Most study participants (62.7%) reported MC being overall effective. Common benefits included reduced pain intensity, anxiety, and dependency on pain and psychiatric medications. Improvements in physical functioning, sleep quality, and mood were reported. Common challenges included difficulty finding a suitable product or dose, experiencing side effects such as ‘undesired high’, ‘stomach issues’, and a limited ‘threshold of pain’ treatable by the product.

Discussion: Findings suggest most participants perceived medical cannabis to be overall effective for chronic pain management. Participants reported improved physical and mental functioning and reduced use of pain and psychiatric medications. Future research systematically assessing side effects, dosage and mode of consumption is needed to further evaluate the outcomes among adults initiating medical cannabis.”

https://pubmed.ncbi.nlm.nih.gov/37484052/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/149