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Abstract: Cannabidiol (CBD) is ubiquitous in state-based medical cannabis programs and consumer products for complementary health or recreational use. CBD has intrinsic pharmacologic effects and associated adverse drug events (ADEs) along with the potential for pharmacokinetic and pharmacodynamic drug–drug interactions (DDIs). Given CBD use among patients with complex conditions and treatment regimens, as well as its expanded consumer use, awareness of potential safety issues with CBD is needed.
Prescribing information for federally approved products containing CBD were reviewed. Data on ADEs and DDIs were extracted and summarized.
Nearly one-half of CBD users experienced ADEs, which displayed a general dose-response relationship. Common ADEs include transaminase elevations, sedation, sleep disturbances, infection, and anemia. Given CBD effects on common biological targets implicated in drug metabolism (e.g., CYP3A4/2C19) and excretion (e.g., P-glycoprotein), the potential for DDIs with commonly used medication is high. General clinical recommendations of reducing substrate doses, monitoring for ADEs, and finding alternative therapy should be considered, especially in medically complex patients. CBD is implicated as both a victim and perpetrator of DDIs and has its own ADE profile. These effects should be considered in the risk-benefit assessment of CBD therapy and patients and consumers made aware of potential safety issues with CBD use.
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Abstract: Tetrahydrocannabinol (THC) is the primary psychoactive ingredient in cannabis… ‘medical’ marijuana programs have increased exposure among medically complex individuals with comorbid conditions and many co-prescribed medications. Thus, THC should be recognized as a pharmacologically complex compound with potential for drug–drug interactions and adverse drug events…
THC also has broad interactions with drug-metabolizing enzymes and can enhance adverse effects of other medications. Pharmacodynamic interactions include neurological effects, impact on the cardiovascular system, and risk of infection. General clinical recommendations for THC use include starting with low doses and titrating to desired effects. However, many interactions may be unavoidable, dose-limiting, or a barrier to THC-based therapy…Meanwhile, clinicians should balance the potential risks of THC and cannabis and the lack of strong evidence of efficacy in many conditions with patient desires for alternative therapy.
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Abstract - Aims: This study was designed to assess links between lifetime levels of marijuana use and accelerated epigenetic aging.
Design: Prospective longitudinal study, following participants annually from age 13 to age 30.
Findings: Lifetime marijuana use predicted accelerated epigenetic aging, with effects remaining even after covarying cell counts, demographic factors and chronological age (β's = 0.32 & 0.27, p's < 0.001, 95% CI's = 0.21-0.43 & 0.16-0.39 for DNAmGrimAge and DunedinPoAm, respectively). Predictions remained after accounting for cigarette smoking (β's = 0.25 & 0.21, respectively, p's < 0.001, 95% CI's = 0.14-0.37 & 0.09-0.32 for DNAmGrimAge and DunedinPoAm, respectively). A dose-response effect was observed and there was also evidence that effects were dependent upon recency of use. Effects of marijuana use appeared to be fully mediated by hypomethylation of a site linked to effects of hydrocarbon inhalation (cg05575921).
Conclusions: Marijuana use predicted epigenetic changes linked to accelerated aging, with evidence suggesting that effects may be primarily due to hydrocarbon inhalation among marijuana smokers. Further research is warranted to explore mechanisms underlying this linkage.
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- Cannabis Causing Cancer Part 1 - Epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003–2017: Part 1: Complete Research here https://rdcu.be/cKfKp
Conclusion: Data suggest that cannabinoids including THC and cannabidiol are important community carcinogens exceeding the effects of tobacco or alcohol. Testicular, (prostatic) and ovarian tumours indicate mutagenic corruption of the germline in both sexes; pediatric tumourigenesis confirms transgenerational oncogenesis; quantitative criteria implying causality are fulfilled.
- Cannabis Causing Cancer Part 2 - Epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003–2017: Part 2: Complete Research here https://rdcu.be/cKfKq
Conclusion: Data implicate 23/28 cancers as being linked with THC or cannabidiol exposure with epidemiologically causal relationships comparable to those for tobacco. AFE-attributable cases for cannabinoids (91,677 and 48,510) compare with PAR-attributable cases for tobacco (36,450). Cannabinoids constitute an important multivalent community carcinogen.
- Cannabis Causing Cancer Part 3 - Epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003–2017: Part 3: Complete Research here https://rdcu.be/cKfOH
Conclusion: Cannabinoids including THC and cannabidiol are therefore important community carcinogens additive to the effects of tobacco and greatly exceeding those of alcohol. Reproductive tract carcinogenesis necessarily implies genotoxicity and epigenotoxicity of the germ line with transgenerational potential. Pseudoexponential and causal dose-response power functions are demonstrated.
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(Published in Neurology)
TAKE-HOME MESSAGE
- In this AHA Scientific Statement, numerous effects of marijuana on brain health are described. These include the effects of:
1) prenatal cannabinoid exposure as well as abnormal fetal neurotransmission in preclinical models and its impact on neuroanatomic areas associated with cognition and emotional regulation;
2) marijuana use on human cognition focusing on possible structural and functional changes in areas involved in cognition, potential detrimental effects of early cannabis exposure on cognition, and multidomain impact of acute marijuana intoxication; and
3) marijuana use on cerebrovascular disease risk, highlighting an association between cannabis use and increased risk of stroke.
- Overall, cumulative evidence suggests that consumption of marijuana may have detrimental effects on brain health, challenging widely accepted beliefs that marijuana is innocuous.
- Global Risks of Cannabis Commercialization – The Manipulative Marketing to Women
- Marijuana & Aging – The Epigenetic Impact (2022)
- Effect of Medical Marijuana Card Ownership on Pain, Insomnia, and Affective Disorder Symptoms in Adults: A Randomized Clinical Trial
- Cannabis, Ageing & Increasing Pressure on Public Health