Monthly Archives: November 2023

Cannabidiol protects the liver from α-Amanitin-induced apoptosis and oxidative stress through the regulation of Nrf2

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“α-Amanitin, the primary lethal toxin of Amanita, specifically targets the liver, causing oxidative stress, hepatocyte apoptosis, and irreversible liver damage. As little as 0.1 mg/kg of α-amanitin can be lethal for humans, and there is currently no effective antidote for α-amanitin poisoning. Cannabidiol is a non-psychoactive natural compound derived from Cannabis sativa that exhibits a wide range of anti-inflammatory, antioxidant, and anti-apoptotic effects. It may play a protective role in preventing liver damage induced by α-amanitin. To investigate the potential protective effects of cannabidiol on α-amanitin-induced hepatocyte apoptosis and oxidative stress, we established α-amanitin exposure models using C57BL/6J mice and L-02 cells in vitro. Our results showed that α-amanitin exposure led to oxidative stress, apoptosis, and DNA damage in both mouse hepatocytes and L-02 cells, resulting in the death of mice. We also found that cannabidiol upregulated the level of Nrf2 and antioxidant enzymes, alleviating apoptosis, and oxidative stress in mouse hepatocytes and L-02 cells and increasing the survival rate of mice. Our findings suggest that cannabidiol has hepatoprotective effects through the regulation of Nrf2 and antioxidant enzymes and may be a potential therapeutic drug for Amanita poisoning.”

https://pubmed.ncbi.nlm.nih.gov/37992955/

https://www.sciencedirect.com/science/article/abs/pii/S0278691523005987?via%3Dihub

Real-Life Experience With Purified Cannabidiol Treatment for Refractory Epilepsy: A Multicenter Retrospective Study

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“Background: Drug-resistant epilepsy (DRE) affects the development and quality of life of children and young adults. We analyzed the effectiveness and safety of purified CBD in this population.

Methods: A retrospective analysis of medical records of 139 children and young adults (54.7% female, median age 12.0 years) with DRE treated with purified CBD from 2018 to 2022 at five medical centers in Israel.

Results: The most common diagnosis was Lennox-Gastaut syndrome (37.4%) followed by Dravet syndrome (16.5%) and tuberous sclerosis complex (16.5%). Median purified CBD dose was 12.5 mg/kg (range 2.5 to 20.0), and median treatment duration was 9.0 months (range 0.5 to 48.0). Most patients (92.2%) had a reduced seizure frequency following treatment initiation; 41.1% had >50% reduction. Fifty-three patients (38.1%) had positive effects: improved alertness (31.7%), improved speech (10.1%), and achievement of new developmental milestones (2.2%). A multivariate linear model assessing predictive factors for seizure reduction demonstrated that patients previously treated with CBD oils, especially those with >50% seizure reduction on prior treatment, were also more likely to have a reduced seizure frequency while they were treated with purified CBD (P = 0.01, P < 0.0001). Development, diagnosis, age, purified CBD dose (0 to 10 mg/kg/day vs 10 to 20 mg/kg/day), and concomitant treatment with clobazam, valproic acid, or everolimus did not affect seizure reduction by purified CBD. The most common adverse events were irritability (20.9%) and drowsiness (12.9%).

Conclusion: Purified CBD is well-tolerated and effective in reducing seizure frequency in children and young adults with DRE.”

https://pubmed.ncbi.nlm.nih.gov/37995414/

https://www.pedneur.com/article/S0887-8994(23)00362-4/fulltext

Cannabidiol Anticonvulsant Effects Against Lithium-Pilocarpine-Induced Status Epilepticus in Male Rats Are Mediated by Neuroinflammation Modulation and Cannabinoids 1 (CB1), But Not CB2 and GABAA Receptors

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“Background: Status epilepticus (SE) is a series of seizures that can lead to serious neurological damages. Cannabidiol (CBD) is extracted from the cannabis plant, which has been approved as an antiseizure medication. This study aimed to determine the efficacy of various doses of CBD on lithium-pilocarpine-induced SE in rats and possible involvement of multiple pharmacological pathways. We hypothesized that cannabinoid receptors type 1 (CB1) and CB2, as well as GABAA receptors, might have important roles in the anticonvulsant effects of CBD against SE by its anti-inflammatory effects. 

Methods: SE was induced by intraperitoneal (i.p.) injection of lithium (127 mg/kg, i.p.) and pilocarpine (60 mg/kg, i.p., 20 h after lithium). Forty-two male rats were divided into seven groups (including control and sham groups), and the treated groups received different doses of CBD (1, 3, 5, 10, and 25 mg/kg, i.p.). SE score was recorded over the next 2 h following pilocarpine injection. Then, we measured the levels of pro-inflammatory cytokines, including interleukin (IL)-lβ and tumor necrosis factor (TNF)-α, using ELISA kits. Also we analyzed the expression of CB1, CB2, and GABAA receptors using the Western blot technique. 

Results: CBD at 5 mg/kg significantly reduced Racine’s scale and duration of seizures, and increased the onset time of seizure. Moreover, CBD 5 mg/kg caused significant reductions in the elevated levels of IL-lβ and TNF-α, as well as a significant increase in the decreased level of CB1 receptor expression compared to the control group. In other word, CBD reverted the effects of SE in terms of neuroinflammation and CB1 receptor. Based on the obtained results, CBD was not able to restore the declined levels of CB2 or GABAA receptors. 

Conclusion: Our study found anticonvulsant effects of CBD on the SE rat model induced by lithium-pilocarpine with probable involvement of CB1 receptors and anti-inflammatory effects by reducing IL-1β and TNF-α markers independent of CB2 and GABAA receptors.”

https://pubmed.ncbi.nlm.nih.gov/37976207/

https://www.liebertpub.com/doi/10.1089/can.2023.0067

Prospective affirmative therapeutics of cannabidiol oil mitigates doxorubicin-induced abnormalities in kidney function, inflammation, and renal tissue changes

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“Nephropathy is the decline in kidney function. A promising treatment for numerous types of illness is using natural materials as natural chemical compounds. The inquiry was conducted to investigate cannabidiol (CBD) potential for renal syndrome protection. The five equal groups of fifty male Sprague-Dawley rats weighing 150 ± 25 g each were designed; group I received distilled water orally, while group II got an intraperitoneal injection of doxorubicin (18 mg/kg bwt). Group III received CBD (26 mg/kg bwt) orally, while group IV received 1 ml of CBD (26 mg/kg bwt) and group V received trimetazidine (10 mg/kg bwt), in addition to a single intraperitoneal dose of doxorubicin (18 mg/kg bwt) on the 11th day for both groups (IV, V). The administration of CBD (26 mg/kg bwt) led to a noticeable improvement in oxidative stress parameters (SOD and GSH) in rats by significantly lowering enzyme activity (ALT and AST), as well as serum creatinine and urea, IL-6, and MDA, confirming the anti-inflammatory accuracy of CBD linked to significant lowering to IL6R DNA frequency concentration in line with histopathology results. As a result of its anti-inflammatory and antioxidant capabilities, cannabidiol may have protective quality, and CBD medication could be related to controlling renal problems.”

https://pubmed.ncbi.nlm.nih.gov/37971510/

https://link.springer.com/article/10.1007/s00210-023-02836-4

Unlocking the Healing Potential: Cannabinoids in Spine Surgery for Pain Relief and Recovery

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“Cannabinoids, such as D9-tetrahydrocannabinol and cannabidiol, interact with endocannabinoid receptors in the central nervous system and immune system, potentially offering pain relief. The entourage effect, resulting from the interaction of multiple cannabis components, may enhance therapeutic impact and efficacy, making them promising candidates for exploring pain relief in spine operations, known to be among the most painful operative procedures.» The use of cannabinoids in pain management requires careful consideration of safety, including their cognitive and psychomotor effects, potential cardiovascular risks, risk of dependence, mental health implications, and drug interactions.» Few studies have analyzed cannabinoid use in relation to spine surgery, with variable results reported, indicating possible effects on reoperation rates, mortality, complications, postoperative opioid use, and length of hospital stay.» Current knowledge gaps exist in the understanding of cannabinoid effects on spine surgery, including the exploration of different administration routes, timing, dosage, and specific outcomes. In addition, mechanistic explanations for the observed results are lacking.» Ethical considerations related to informed consent, medical expertise, societal impact, and legal compliance must also be thoroughly addressed when considering the utilization of cannabinoids in spinal pathologies and back pain treatment.”

https://pubmed.ncbi.nlm.nih.gov/37972215/

https://journals.lww.com/jbjsreviews/abstract/2023/11000/unlocking_the_healing_potential__cannabinoids_in.4.aspx

Medical cannabis for refractory cancer-related pain in a specialised clinical service: a cross-sectional study

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“Background and objectives: Cancer-related pain management in advanced stages presents a significant challenge that often requires a multidisciplinary approach. Although advancements in pharmacological and interventional therapies, a considerable number of patients still suffer from refractory pain, leading to unmet clinical needs. This study shares our experience with medical cannabis (MC) as a potential therapy for this specific population of patients with cancer-related refractory pain.

Methods: In a cross-sectional study, 252 consecutive refractory cancer-related pain patients (mean age=61.71, SD=14.02, 47.6% males) filled out detailed self-report questionnaires. Of these, 126 patients (55%) were treated with MC and 105 patients (45%) were not.

Results: Most patients received pain management from their oncologist, not a pain specialist. MC was mainly started for pain relief, sleep difficulties and anorexia. About 70% of patients reported subjective improvement from MC, with almost 40% reporting a significant improvement in coping with their illness. Side effects were generally mild, with fatigue and dizziness being the most common (21.78% and 23.46%, respectively). No patient required dedicated medical care for side effects. Of non-users, 65% had tried MC before and stopped due to lack of effectiveness or side effects (39.7% and 34.6%, respectively).

Conclusion: Refractory cancer pain necessitates innovative approaches. This registry highlights that MC can effectively improve symptoms in non-responsive patients, with favourable safety profiles for this vulnerable population.”

https://pubmed.ncbi.nlm.nih.gov/37973200/

https://spcare.bmj.com/content/early/2023/11/15/spcare-2023-004421

Engineering cannabidiol synergistic carbon monoxide nanocomplexes to enhance cancer therapy via excessive autophagy

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“Although carbon monoxide (CO)-based treatments have demonstrated the high cancer efficacy by promoting mitochondrial damage and core-region penetrating ability, the efficiency was often compromised by protective autophagy (mitophagy). Herein, cannabidiol (CBD) is integrated into biomimetic carbon monoxide nanocomplexes (HMPOC@M) to address this issue by inducing excessive autophagy. The biomimetic membrane not only prevents premature drugs leakage, but also prolongs blood circulation for tumor enrichment. After entering the acidic tumor microenvironment, carbon monoxide (CO) donors are stimulated by hydrogen oxide (H2O2) to disintegrate into CO and Mn2+. The comprehensive effect of CO/Mn2+ and CBD can induce ROS-mediated cell apoptosis. In addition, HMPOC@M-mediated excessive autophagy can promote cancer cell death by increasing autophagic flux via class III PI3K/BECN1 complex activation and blocking autolysosome degradation via LAMP1 downregulation. Furthermore, in vivo experiments showed that HMPOC@M+ laser strongly inhibited tumor growth and attenuated liver and lung metastases by downregulating VEGF and MMP9 proteins. This strategy may highlight the pro-death role of excessive autophagy in TNBC treatment, providing a novel yet versatile avenue to enhance the efficacy of CO treatments. Importantly, this work also indicated the applicability of CBD for triple-negative breast cancer (TNBC) therapy through excessive autophagy.”

https://pubmed.ncbi.nlm.nih.gov/37969731/

“In our points, this comprehensive strategy will open a new door for efficient triple-negative breast cancer therapy through CBD-induced excessive autophagy.”

https://www.sciencedirect.com/science/article/pii/S2211383523001648?via%3Dihub

The psychedelic effects of cannabis: A review of the literature

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“Cannabis and classic psychedelics are controlled substances with emerging evidence of efficacy in the treatment of a variety of psychiatric illnesses. Cannabis has largely not been regarded as having psychedelic effects in contemporary literature, despite many examples of historical use along with classic psychedelics to attain altered states of consciousness.

Research into the “psychedelic” effects of cannabis, and delta-9-tetrahydrocannabinol (THC) in particular, could prove helpful for assessing potential therapeutic indications and elucidating the mechanism of action of both cannabis and classic psychedelics.

This review aggregates and evaluates the literature assessing the capacity of cannabis to yield the perceptual changes, aversiveness, and mystical experiences more typically associated with classic psychedelics such as psilocybin. This review also provides a brief contrast of neuroimaging findings associated with the acute effects of cannabis and psychedelics.

The available evidence suggests that high-THC cannabis may be able to elicit psychedelic effects, but that these effects may not have been observed in recent controlled research studies due to the doses, set, and settings commonly used. Research is needed to investigate the effects of high doses of THC in the context utilized in therapeutic studies of psychedelics aimed to occasion psychedelic and/or therapeutic experiences.

If cannabis can reliably generate psychedelic experiences under these conditions, high-THC dose cannabis treatments should be explored as potential adjunctive treatments for psychiatric disorders and be considered as an active comparator in clinical trials involving traditional psychedelic medications.”

https://pubmed.ncbi.nlm.nih.gov/37947321/

https://journals.sagepub.com/doi/10.1177/02698811231209194

“Psychedelic drugs in the treatment of psychiatric disorders”

https://pubmed.ncbi.nlm.nih.gov/37615227/

Improved Post-Traumatic Stress Disorder Symptoms and Related Sleep Disturbances after Initiation of Medical Marijuana Use: Evidence from a Prospective Single Arm Pilot Study

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“Introduction: Post-traumatic stress disorder (PTSD) is a debilitating disorder experienced by a subgroup of individuals following a life-threatening trauma. Several US states have passed laws permitting the medical use of marijuana (MMJ) by individuals with PTSD, despite very little scientific indication on the appropriateness of marijuana as a therapy for PTSD. This prospective pilot study of adults with confirmed PTSD in Florida (FL) investigated whether PTSD symptoms, sleep quality, affect, and general physical and mental health/well-being improved post-initiation of MMJ treatment.

Methods: Participants, N = 15, were recruited from two MMJ clinics in Gainesville and Jacksonville, FL. To be eligible, participants had to be 18 years of age or older, not currently on MMJ, and willing to abstain from recreational marijuana, if using any, until the State Medical Cannabis Card was obtained, screen positive for PTSD. Participants were assessed at baseline (pre-MMJ initiation) and 30 and 70 days post-MMJ initiation using the Pittsburgh Sleep Quality Index (PSQI), PTSD Checklist for DSM-5 (PCL-5), Positive and Negative Affect Schedule (PANAS), PROMIS Global Health V1.2, and semi-structured marijuana and other substance use assessment.

Results: PTSD symptom severity as measured by total PCL-5 score improved significantly at 30- and 70-day follow-ups. Similarly, statistically significant reductions in nightmares were reported at 30- and 70-day follow-ups. Corresponding improvements in sleep were noticed with participants reporting increased duration of sleep hours, sleep quality, sleep efficiency, and total PSQI score. Likewise, negative affect and global mental health improved significantly at follow-up. According to the post hoc analyses, the most statistically significant changes occurred between baseline and 30-day follow-up. The exception to this pattern was nightmares, which did not show significant improvement until day 70.

Conclusion: The findings of this study highlight the potential of MMJ in improving patient outcomes for those with PTSD, particularly concerning sleep disturbances, which often do not respond to currently available treatments.”

https://pubmed.ncbi.nlm.nih.gov/37965569/

https://karger.com/mca/article/6/1/160/869732/Improved-Post-Traumatic-Stress-Disorder-Symptoms

Effects of Two Cannabidiol Oil Products on Self-Reported Stress Relief: A Quasi-Experimental Study

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“Introduction: Estimated rates of past-month cannabidiol (CBD) use in the general public are 13-26% and emerging research examines CBD as a potential adjunct treatment for several medical conditions, including stress-related disorders (e.g., depression, anxiety, and chronic pain). However, little is known about the effects of different CBD products on self-reported stress. The present study compared the effects of two delta-9-tetrahydrocannabinol (THC)-free CBD tincture products – (1) an isolate CBD oil and (2) a broad spectrum CBD oil – on self-ratings of effectiveness of the product and ability to manage stress.

Methods: This quasi-experimental study reports on a total of 374 participants who completed either a 30- or 60-day regimen. Participants were instructed to use a 1,000 mg CBD isolate product at will, and then switch over to a 1,000 mg broad spectrum product for the remainder of the regimen (i.e., next 15 or 30 days). Self-reported effectiveness of the product and its ability to help manage stress was compared between the isolate and broad spectrum products. We also examined overall impression, quality, taste, and adverse effects of each product.

Results: Overall, both products were rated to be highly effective and able to assist with stress management. Participants reported that the broad spectrum product’s effectiveness (p < 0.001) and ability to reduce stress (p < 0.001) as greater than the isolate product across both regimens. However, participants preferred the taste of the isolate product over that of the broad spectrum across regimens (p < 0.05). For the 30-day regimen, participants reported a more positive overall impression of the isolate as compared to the broad spectrum (p < 0.001); however, overall impression did not differ between the products in the 60-day regimen. There was no difference in adverse effects or quality between the products, across both regimens.

Conclusion: These results fit with prior studies suggesting anti-stress effects of CBD. Ratings were higher for the broad spectrum as compared to the isolate product, which is consistent with prior data suggesting that cannabinoids can work synergistically to maximize benefits. Nonetheless, more controlled studies are needed to explore these effects in nonclinical and clinical populations.”

https://pubmed.ncbi.nlm.nih.gov/37942294/

https://karger.com/mca/article/6/1/138/869446/Effects-of-Two-Cannabidiol-Oil-Products-on-Self