Tag Archives: THC

Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer.

Posted on by
Reply

 ijms-logo“Cannabis sativa L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present in Cannabis sativa L., namely, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different types of cancer. The main focus is on the latest in vitro and in vivo studies that present data regarding the anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD together with their mechanisms of action. The latest clinical evidence of the anticancer effects of CBD is also outlined. Moreover, the main aspects of the pharmacological and toxicological profiles are given.”

https://www.ncbi.nlm.nih.gov/pubmed/31775230

https://www.mdpi.com/1422-0067/20/23/5905

Δ9-THC and related cannabinoids suppress substance P- induced neurokinin NK1-receptor-mediated vomiting via activation of cannabinoid CB1 receptor.

Posted on by
Reply

European Journal of Pharmacology

“Δ9-THC suppresses cisplatin-induced vomiting through activation of cannabinoid CB1 receptors.

Cisplatin-evoked emesis is predominantly due to release of serotonin and substance P (SP) in the gut and the brainstem which subsequently stimulate their corresponding 5-HT3-and neurokinin NK1-receptors to induce vomiting. Δ9-THC can inhibit vomiting caused either by the serotonin precursor 5-HTP, or the 5-HT3 receptor selective agonist, 2-methyserotonin.

In the current study, we explored whether Δ9-THC and related CB1/CB2 receptor agonists (WIN55,212-2 and CP55,940) inhibit vomiting evoked by SP (50 mg/kg, i.p.) or the NK1 receptor selective agonist GR73632 (5 mg/kg, i.p.). Behavioral methods were employed to determine the antiemetic efficacy of cannabinoids in least shrews.

Our results showed that administration of varying doses of Δ9-THC (i.p. or s.c.), WIN55,212-2 (i.p.), or CP55,940 (i.p.) caused significant suppression of SP-evoked vomiting in a dose-dependent manner. When tested against GR73632, Δ9-THC also dose-dependently reduced the evoked emesis.

The antiemetic effect of Δ9-THC against SP-induced vomiting was prevented by low non-emetic doses of the CB1 receptor inverse-agonist/antagonist SR141716A (<10 mg/kg). We also found that the NK1 receptor antagonist netupitant can significantly suppress vomiting caused by a large emetic dose of SR141716A (20 mg/kg).

In sum, Δ9-THC and related cannabinoids suppress vomiting evoked by the nonselective (SP) and selective (GR73632) neurokinin NK1 receptor agonists via stimulation of cannabinoid CB1 receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/31738934

https://www.sciencedirect.com/science/article/pii/S0014299919307587?via%3Dihub

Short- and Long-Term Effects of Cannabis on Headache and Migraine.

Posted on by
Reply

“Use of cannabis to alleviate headache and migraine is relatively common, yet research on its effectiveness remains sparse.

We sought to determine whether inhalation of cannabis decreases headache and migraine ratings as well as whether gender, type of cannabis (concentrate vs. flower), THC, CBD, or dose contribute to changes in these ratings. Finally, we explored evidence for tolerance to these effects.

Archival data were obtained from StrainprintTM, a medical cannabis app that allows patients to track symptoms before and after using different strains and doses of cannabis. Latent change score models and multilevel models were used to analyze data from 12,293 sessions where cannabis was used to treat headache and 7,441 sessions where cannabis was used to treat migraine.

There were significant reductions in headache and migraine ratings after cannabis use.

Men reported larger reductions in headache than women and use of concentrates was associated with larger reductions in headache than flower. Further, there was evidence of tolerance to these effects.

Perspective: Inhaled cannabis reduces self-reported headache and migraine severity by approximately 50%. However, its effectiveness appears to diminish across time and patients appear to use larger doses across time, suggesting tolerance to these effects may develop with continued use.”

https://www.ncbi.nlm.nih.gov/pubmed/31715263

“Headache and migraine ratings were reduced by nearly 50% after using cannabis.”

https://www.jpain.org/article/S1526-5900(19)30848-X/fulltext

Inhibition of tremulous jaw movements in rats by memantine-Δ9 -tetrahydrocannabinol combination: neuroanatomical correlates.

Posted on by
Reply

British Journal of Pharmacology banner“Memantine and marijuana smoking have been previously found to inhibit tremor in parkinsonian patients, however, the observed effects were relatively weak. The tremorolytic efficacy of memantine and cannabinoid co-administration is unstudied.

This work aimed to evaluate antitremor activity of memantine-Δ9 -tetrahydrocannabinol combination; additionally, the involvement of some neuroanatomical structures in the regulation of the combination effect was evaluated.

EXPERIMENTAL APPROACH:

Haloperidol-induced tremulous jaw movements in rats were used as a model of parkinsonian-like tremor. To evaluate the role of central receptor systems in the drug effect, receptor-targeting agents were administered locally into certain brain areas.

KEY RESULTS:

Memantine and Δ9 -tetrahydrocannabinol alone were without effect, however, co-administration of the drugs significantly decreased number of haloperidol-induced jaw movements. The antitremor activity of the combination was antagonized (i) by injections of L-glutamate into the dorsal striatum, entopeduncular nucleus, substantia nigra pars reticulata, globus pallidus, supratrigeminal and trigeminal motor nuclei but not into the subthalamic and cuneiform nuclei; (ii) by injections of CGS 21680 into the ventrolateral striatum; (iii) by injections of bicuculline into the rostral part of the parvicellular reticular nucleus.

CONCLUSION AND IMPLICATIONS:

Memantine and Δ9 -tetrahydrocannabinol supra-additively inhibit haloperidol-induced tremulous jaw movements. Apparently, the co-administration of the drugs might be a new approach to the treatment of tremor. The presented results identify brain areas influencing parkinsonian-like tremor in rats; these data can help advance the development of novel treatments for repetitive involuntary movements.”

https://www.ncbi.nlm.nih.gov/pubmed/31696510

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14914

“Memantine is a prescription drug used to treat moderate to severe confusion (dementia) related to Alzheimer’s disease. Memantine is available under the following different brand names: Namenda XR, and Namenda.”  https://www.rxlist.com/consumer_memantine_namenda/drugs-condition.htm

Cannabidiol Regulates Gene Expression in Encephalitogenic T cells Using Histone Methylation and noncoding RNA during Experimental Autoimmune Encephalomyelitis.

Posted on by
Reply

 Scientific Reports“Cannabidiol (CBD) has been shown by our laboratory to attenuate experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).

In this study, we used microarray and next generation sequencing (NGS)-based approaches to determine whether CBD would alter genome-wide histone modification and gene expression in MOG sensitized lymphocytes.

In summary, this study demonstrates that CBD suppresses inflammation through multiple mechanisms, from histone methylation to miRNA to lncRNA.”

https://www.ncbi.nlm.nih.gov/pubmed/31673072

“Marijuana (Cannabis sativa) has many biologically active compounds and its medicinal value has been known for centuries. CBD has been shown to have an anti-inflammatory effect in several animal models. In immune system, studies from our lab as well as those from others have shown that both THC and CBD have anti-inflammatory properties. ”

https://www.nature.com/articles/s41598-019-52362-8

Prevalence and predictors of cannabis use among men receiving androgen-deprivation therapy for advanced prostate cancer.

Posted on by
Reply

 “Prostate cancer patients receiving androgen-deprivation therapy (ADT) often experience a combination of disease symptoms and treatment side effects. The therapeutic use of cannabis to alleviate these side effects has not been studied, despite increasing patient interest. With the increasing availability of cannabis, it is important for clinicians to understand the prevalence, predictors, and perceived benefits of cannabis use among patients with prostate cancer.

RESULTS:

Questionnaire data revealed that 23.2% of surveyed men had recently used cannabis. In contrast, 5.8% of men had detectable levels of THC metabolite in their urine. Combined questionnaire and urine data revealed that cannabis users were significantly younger (p=0.003) and had lower testosterone levels (p=0.003) than non-users. The majority of men experiencing common ADT side effects reported some degree of relief following cannabis use.

CONCLUSIONS:

Cannabis use among men with advanced prostate cancer receiving ADT is more prevalent than in the general population and the majority of other oncological cohorts. Lower testosterone levels and reported therapeutic benefit among cannabis users warrants confirmation in appropriate clinical trials.”

https://www.ncbi.nlm.nih.gov/pubmed/31658007

https://cuaj.ca/index.php/journal/article/view/5911

A role for cannabinoids in the treatment of myotonia? Report of compassionate use in a small cohort of patients.

Posted on by
Reply

“The symptomatic treatment of myotonia and myalgia in patients with dystrophic and non-dystrophic myotonias is often not satisfactory.

Some patients anecdotally report symptoms’ relief through consumption of cannabis.

METHODS:

A combination of cannabidiol and tetrahydrocannabinol (CBD/THC) was prescribed as compassionate use to six patients (four patients with myotonic dystrophy types 1 and 2, and 2 patients with CLCN1-myotonia) with therapy-resistant myotonia and myalgia. CBD/THC oil was administered on a low dose in the first 2 weeks and adjusted to a higher dose in the following 2 weeks. Myotonia behaviour scale (MBS), hand-opening time, visual analogue scales (VAS) for myalgia and myotonia, and fatigue and daytime sleepiness severity scale (FSS, ESS) were performed weekly to monitor treatment response.

RESULTS:

All patients reported an improvement of myotonia especially in weeks 3 and 4 of treatment: MBS improved of at least 2 points in all patients, the hand-opening time variously improved in 5 out of 6 patients. Chronic myalgia was reported by both DM2 patients at baseline, one of them experienced a significant improvement of myalgia under treatment. Some gastrointestinal complaints, as abdominal pain and diarrhoea, improved in 3 patients; however, 4 out of 6 patients reported new-onset constipation. No other relevant side effect was noticed.

CONCLUSIONS:

These first empirical results suggest a potentially beneficial role of CBD/THC in alleviating myotonia and should encourage further research in this field including a randomized-controlled trial on larger cohorts.”

https://www.ncbi.nlm.nih.gov/pubmed/31655890

https://link.springer.com/article/10.1007%2Fs00415-019-09593-6

“Myotonia is a medical term that refers to a neuromuscular condition in which the relaxation of a muscle is impaired.” https://www.ninds.nih.gov/Disorders/All-Disorders/Myotonia-Information-Page

Effects of Cannabis and Its Components on the Retina: A Systematic Review.

Posted on by
Reply

 Publication Cover“Cannabis is the most prevalent drug in the world and its consumption is growing. Cannabinoid receptors are present in the human central nervous system. Recent studies show evidence of the effects of cannabinoids on the retina, and synthesizing the results of these studies may be relevant for ophthalmologists. Thus, this review adopts standardized, systematic review methodology to investigate the effects of exposure to cannabis and components on the retina.

RESULTS:

We retrieved 495 studies, screened 229 studies, assessed 52 studies for eligibility, and included 16 studies for qualitative analysis. The cannabinoids most frequently investigated were delta-9-tetrahydrocannabinol (THC), abnormal cannabidiol, synthetic cannabinoid, and cannabidiol (CDB). The outcomes most studied were neuroretinal dysfunction, followed by vascular effects. The studies also included investigation of neuroprotective and anti-inflammatory effects and teratogenic effects.

CONCLUSIONS:

This review suggests that cannabinoids may have an important role in retinal processing and function.”

https://www.ncbi.nlm.nih.gov/pubmed/31648567

https://www.tandfonline.com/doi/abs/10.1080/15569527.2019.1685534?journalCode=icot20

Acute and residual effects of smoked cannabis: Impact on driving speed and lateral control, heart rate, and self-reported drug effects

Posted on by
Reply

 Drug and Alcohol Dependence“Although driving under the influence of cannabis is increasingly common among young adults, little is known about residual effects on driver behavior.

This study examined acute and residual effects of smoked cannabis on simulated driving performance of young cannabis users.

Methods

In this double-blind, placebo-controlled, parallel-group randomized clinical trial, cannabis users (1-4 days/week) aged 19-25 years were randomized with a 2:1 allocation ratio to receive active (12.5% THC) or placebo (0.009% THC) cannabis in a single 750 mg cigarette. A median split (based on whole-blood THC concentrations at the time of driving) was used to divide the active group into low and high THC groups. Our primary outcome was simulated driving performance, assessed 30 minutes and 24 and 48 hours after smoking. Secondary outcomes included blood THC concentrations, subjective drug effects, and heart rate.

Results

Ninety-six participants were randomized, and 91 were included in the final analysis (30 high THC, 31 low THC, 30 placebo). Mean speed (but not lateral control) significantly differed between groups 30 minutes after smoking cannabis (p ≤ 0.02); low and high THC groups decreased their speed compared to placebo. Heart rate, VAS drug effect and drug high increased significantly immediately after smoking cannabis and declined steadily after that. There was little evidence of residual effects in any of the measures.

Conclusion

Acutely, cannabis caused decreased speed, increased heart rate, and increases in VAS drug effect and drug high. There was no evidence of residual effects on these measures over the two days following cannabis administration.

Smoked cannabis (12.5% THC) led to an acute decrease in speed in young adults. There was no clear effect of smoked cannabis on lateral control. There was little evidence of residual effects of smoked cannabis on driving performance.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871619304181

‘Standard THC Units’: a proposal to standardise dose across all cannabis products and methods of administration.

Posted on by
Reply

Publication cover image“Cannabis products are becoming increasingly diverse, and they vary considerably in concentrations of ∆9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). Higher doses of THC can increase the risk of harm from cannabis, while CBD may partially offset some of these effects. Lower Risk Cannabis Use Guidelines currently lack recommendations based on quantity of use, and could be improved by implementing standard units. However, there is currently no consensus on how units should be measured or standardised across different cannabis products or methods of administration.

ARGUMENT:

Existing proposals for standard cannabis units have been based on specific methods of administration (e.g. joints) and these may not capture other methods including pipes, bongs, blunts, dabbing, vaporizers, vape pens, edibles and liquids. Other proposals (e.g. grams of cannabis) cannot account for heterogeneity in THC concentrations across different cannabis products. Similar to alcohol units, we argue that standard cannabis units should reflect the quantity of active pharmacological constituents (dose of THC). On the basis of experimental and ecological data, public health considerations, and existing policy we propose that a ‘Standard THC Unit’ should be fixed at 5 milligrams of THC for all cannabis products and methods of administration. If supported by sufficient evidence in future, consumption of Standard CBD Units might offer an additional strategy for harm reduction.

CONCLUSIONS:

Standard THC Units can potentially be applied across all cannabis products and methods of administration to guide consumers and promote safer patterns of use.”

https://www.ncbi.nlm.nih.gov/pubmed/31606008

https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14842