Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Medical Cannabis Use Reduces Opioid Prescriptions in Patients With Chronic Back Pain

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“This study investigates whether the use of medical cannabis (MC) in patients with chronic back pain is associated with a decreased opioid prescription.

Results

Patients who started at less than 15 MME/day and patients who started at greater than 15 MME/day decreased from 15.1 to 11.0 (n = 186, p < 0.01), 3.5 to 2­­­.1 (n = 134, p < 0.01), and 44.9 to 33.9 (n = 52, p < 0.01), respectively. Pain and disability scores were improved at follow-up as well.

Conclusion

MC use reduces opioid prescription for patients with chronic back pain and improves pain and disability scores.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860705/

Medical Cannabis Use Reduces Opioid Prescriptions in Patients With Osteoarthritis

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“Osteoarthritis (OA) can result in significant pain, requiring pain management with opioids. Medical cannabis (MC) has the potential to be an alternative to opioids for chronic pain conditions. This study investigates whether MC used in the management of OA-related chronic pain can reduce opioid utilization.

Results

Average MME/day decreased from 18.2 to 9.8 (n=40, p<0.05). The percentage of patients who dropped to 0 MME/day was 37.5%. VAS scores decreased significantly at three and six months, and Global Physical Health score increased significantly by three months.

Conclusions

MC reduces opioid prescription for patients with chronic OA pain and improves pain and quality of life.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8873278/

[Cannabinoids reduce opioid use in older patients with pain : Retrospective three-year analysis of data from a general practice]

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“Background: Relevant data for the prescription and therapeutic effects of medical cannabinoids (CAM) are still missing in everyday medicine especially for elderly and geriatric patients.

Aim of the study: Documentation of prescription (duration, age) of CAM (dronabinol, nabiximols, cannabinoid extracts) and co-medicated opioids in a doctor’s office specializing in pain.

Methods: Analysis of the consumption of opioids (morphine equivalent) and CAM (THC equivalent) for age and gender.

Results: In all, 178 patients with chronic pain were treated for a period of 366 days (median; range 31-2590 days). Median age was 72 years (26-96 years); 115 were women (64.8%). Of these, 34 were younger than 65 years, 42 were 65-80 years and 40 were more than 80 years old. Of the 63 men, 29 were younger than 65 years, 24 were 65-80 years and 10 were older than 80 years. Indications for CAM were chronic pain and the limitations for opioids because of side effects and worsening of quality of life. To total of 1001 CAM were prescribed, 557 (55.6%) dronabinol as liquid, 328 (32.7%) as full spectrum extracts and 66 (6.6%) as oro-mucosal nabiximols spray. 50 prescriptions (5%) contained more than one CAM simultaneously. The daily consumption of dronabinol liquor and extracts were 9.6 mg/day (median), and of spray 13.6 mg. The dosage over time did not change in patients older than 64; in younger patients, there was a non-significant increasing trend. Women requested lower THC dosages compared to men (8.1 mg vs. 14.8 mg). Furthermore, 10 patients (5.6%) stopped CAM because of failing effectivity, 7 (3.9%) because of failing cost coverage and only 5 because of adverse side effects. 115 patients (65%) with CAM also received opioids a median 65 mg/day morphine equivalents. This opioid dosage was significantly reduced in course of time by 24 mg/day morphine equivalents or 50%. This reduction was independent on CAM dosage, age and gender.

Discussion: Patients with chronic pain profit from long-term CAM which safely and significantly lower the consumption of comedicated opioids, even at low dosages (< 7.5 mg/day). For women, low-dose THC may be sufficient. Older patients benefit from CAM, and adverse effects do not limit the (chronic) use and prescription of CAM in the elderly.”

https://pubmed.ncbi.nlm.nih.gov/35384481/

Mechanistic origin of partial agonism of tetrahydrocannabinol for cannabinoid receptors

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“Cannabinoid receptor 1 (CB1) is a therapeutically relevant drug target for controlling pain, obesity, and other central nervous system disorders. However, full agonists and antagonists of CB1 have been reported to cause serious side effects in patients. Therefore, partial agonists have emerged as a viable alternative as they can mitigate overstimulation and side effects. One of the key bottlenecks in the design of partial agonists, however, is the lack of understanding of the molecular mechanism of partial agonism itself. In this study, we examine two mechanistic hypotheses for the origin of partial agonism in cannabinoid receptors and predict the mechanistic basis of partial agonism exhibited by Δ9-Tetrahydrocannabinol (THC) against CB1. In particular, we inspect whether partial agonism emerges from the ability of THC to bind in both agonist and antagonist-binding poses or from its ability to only partially activate the receptor. We used extensive molecular dynamics simulations and Markov state modeling to capture the THC binding in both antagonist and agonist-binding poses in the CB1 receptor. Furthermore, we predict that binding of THC in the agonist-binding pose leads to rotation of toggle switch residues and causes partial outward movement of intracellular transmembrane helix 6 (TM6). Our simulations also suggest that the alkyl side chain of THC plays a crucial role in determining partial agonism by stabilizing the ligand in the agonist and antagonist-like poses within the pocket. Taken together, this study provides important insights into the mechanistic origin of the partial agonism of THC.”

https://pubmed.ncbi.nlm.nih.gov/35227761/

Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice

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“Studies on the effective and safe therapeutic dosage of delta-9-tetrahydrocannabinol (THC) for the treatment of Alzheimer’s disease (AD) have been sparse due to the concern about THC’s psychotropic activity. The present study focused on demonstrating the beneficial effect of low-dose THC treatment in preclinical AD models.

The effect of THC on amyloid-β (Aβ) production was examined in N2a/AβPPswe cells. An in vivo study was conducted in aged APP/PS1 transgenic mice that received an intraperitoneal injection of THC at 0.02 and 0.2 mg/kg every other day for three months.

The in vitro study showed that THC inhibited Aβ aggregation within a safe dose range. Results of the radial arm water maze (RAWM) test demonstrated that treatment with 0.02 and 0.2 mg/kg of THC for three months significantly improved the spatial learning performance of aged APP/PS1 mice in a dose-dependent manner.

Results of protein analyses revealed that low-dose THC treatment significantly decreased the expression of Aβ oligomers, phospho-tau and total tau, and increased the expression of Aβ monomers and phospho-GSK-3β (Ser9) in the THC-treated brain tissues.

In conclusion, treatment with THC at 0.2 and 0.02 mg/kg improved the spatial learning of aged APP/PS1 mice, suggesting low-dose THC is a safe and effective treatment for AD.”

https://pubmed.ncbi.nlm.nih.gov/35269905/

https://www.mdpi.com/1422-0067/23/5/2757


Thromboembolic Outcomes in Tetrahydrocannabinol-Positive Trauma Patients With Traumatic Brain Injury

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“Introduction: Traumatic brain injury (TBI) is a significant source of morbidity and mortality in the United States. Recent shifts in state legislation have increased the use of recreational and medical marijuana. While cannabinoids and tetrahydrocannabinol (THC) have known anti-inflammatory effects, the impact of preinjury THC use on clinical outcomes in the setting of severe TBI is unknown. We hypothesized that preinjury THC use in trauma patients suffering TBI would be associated with decreased thromboembolic events and adverse outcomes.

Methods: The American College of Surgeons Trauma Quality Improvement Program was used to identify patients aged ≥18 y with TBI and severe injury (Injury Severity Score ≥ 16) in admit year 2017. Patients with smoking or tobacco history or missing or positive toxicology tests for drug and/or alcohol use other than THC were excluded. Propensity score matching was used to compare THC+ patients to similar THC- patients.

Results: A total of 13,266 patients met inclusion criteria, of which 1669 were THC+. A total of 1377 THC+ patients were matched to 1377 THC- patients. No significant differences were found in in-hospital outcomes, including mortality, length of stay, cardiac arrest, pulmonary embolism, deep vein thrombosis, or acute respiratory distress syndrome. No patients had ischemic stroke, and THC+ patients had significantly decreased rates of hemorrhagic stroke (0.5% versus 1.5%, P = 0.02, odds ratio 0.41 [95% confidence interval 0.18-0.86]).

Conclusions: Preinjury THC use may be associated with decreased hemorrhagic stroke in severely injured patients with TBI, but there was no difference in thromboembolic outcomes. Further research into pathophysiological mechanisms related to THC are needed.”

https://pubmed.ncbi.nlm.nih.gov/35305485/

“THC linked to lower hemorrhagic stroke risk in people with traumatic brain injury”

https://vancouversun.com/cannabis-news/thc-use-may-be-associated-with-lower-hemorrhagic-stroke-risk-in-people-with-traumatic-brain-injury/wcm/a3ae3f22-2b3f-439f-987d-6364c7425eb8/amp/

Administration of Δ 9-Tetrahydrocannabinol Following Controlled Cortical Impact Restores Hippocampal-Dependent Working Memory and Locomotor Function

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“Hypothesis: Administration of the phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) will enhance brain repair and improve short-term spatial working memory in mice following controlled cortical impact (CCI) by upregulating granulocyte colony-stimulating factor (G-CSF) and other neurotrophic factors (brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]) in hippocampus (HP), cerebral cortex, and striatum. Results: Δ9-THC-treated mice exhibited marked improvement in performance on the Y-maze indicating that treatment with the phytocannabinoid could reverse the deficit in working memory caused by the CCI. Δ9-THC-treated mice ran on the rotarod longer than vehicle-treated mice and recovered to normal rotarod performance levels at 2 weeks. Δ9-THC-treated mice, compared with vehicle-treated animals, exhibited significant upregulation of G-CSF as well as BDNF and GDNF in the cerebral cortex, striatum, and HP. Levels of 2-AG were also increased in the Δ9-THC-treated mice. Conclusion: Administration of the phytocannabinoid Δ9-THC promotes significant functional recovery from traumatic brain injury (TBI) in the realms of working memory and locomotor function. This beneficial effect is associated with upregulation of brain 2-AG, G-CSF, BDNF, and GDNF. The latter three neurotrophic factors have been previously shown to mediate brain self-repair following TBI and stroke.”

https://pubmed.ncbi.nlm.nih.gov/34747647/

Impact of Cannabinoid Compounds on Skin Cancer

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“Drugs targeting the endocannabinoid system are of interest as potential systemic chemotherapeutic treatments and for palliative care in cancer.

In this context, cannabinoid compounds have been successfully tested as a systemic therapeutic option in preclinical models over the past decades. Recent findings have suggested an essential function of the endocannabinoid system in the homeostasis of various skin functions and indicated that cannabinoids could also be considered for the treatment and prophylaxis of tumour diseases of the skin.

Cannabinoids have been shown to exert their anticarcinogenic effects at different levels of skin cancer progression, such as inhibition of tumour growth, proliferation, invasion and angiogenesis, as well as inducing apoptosis and autophagy. This review provides an insight into the current literature on cannabinoid compounds as potential pharmaceuticals for the treatment of melanoma and squamous cell carcinoma.”

https://pubmed.ncbi.nlm.nih.gov/35406541/

“Recent research has suggested that the endocannabinoid system offers several pharmacotherapeutic targets for drug administration as new options for the treatment and prophylaxis of skin cancer. This review focused on the anticarcinogenic mechanisms of cannabinoids at the different levels of skin cancer progression, such as inhibition of tumour growth, proliferation, invasion and angiogenesis, as well as inducing apoptosis and autophagy.”

https://www.mdpi.com/2072-6694/14/7/1769


Plant-derived cannabinoids as anticancer agents

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“Substantial preclinical evidence demonstrates the antiproliferative, cytotoxic, and antimetastatic properties of plant-derived cannabinoids (phytocannabinoids) such as cannabidiol and tetrahydrocannabinol. The cumulative body of research into the intracellular mechanisms and phenotypic effects of these compounds supports a logical, judicious progression to large-scale phase II/III clinical trials in certain cancer types to truly assess the efficacy of phytocannabinoids as anticancer agents.”

https://pubmed.ncbi.nlm.nih.gov/35260379/

Cannabinoids as anticancer drugs: current status of preclinical research

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“Drugs that target the endocannabinoid system are of interest as pharmacological options to combat cancer and to improve the life quality of cancer patients. From this perspective, cannabinoid compounds have been successfully tested as a systemic therapeutic option in a number of preclinical models over the past decades. As a result of these efforts, a large body of data suggests that the anticancer effects of cannabinoids are exerted at multiple levels of tumour progression via different signal transduction mechanisms. Accordingly, there is considerable evidence for cannabinoid-mediated inhibition of tumour cell proliferation, tumour invasion and metastasis, angiogenesis and chemoresistance, as well as induction of apoptosis and autophagy. Further studies showed that cannabinoids could be potential combination partners for established chemotherapeutic agents or other therapeutic interventions in cancer treatment. Research in recent years has yielded several compounds that exert promising effects on tumour cells and tissues in addition to the psychoactive Δ9-tetrahydrocannabinol, such as the non-psychoactive phytocannabinoid cannabidiol and inhibitors of endocannabinoid degradation. This review provides an up-to-date overview of the potential of cannabinoids as inhibitors of tumour growth and spread as demonstrated in preclinical studies.”

https://pubmed.ncbi.nlm.nih.gov/35277658/