Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Cannabis sativa L. Bioactive Compounds and Their Protective Role in Oxidative Stress and Inflammation

Posted on by
Reply

“Cannabis (Cannabis sativa L.) plants from the family Cannabidaceae have been used since ancient times, to produce fibers, oil, and for medicinal purposes. Psychoactive delta-9-tetrahydrocannabinol (THC) and nonpsychoactive cannabidiol (CBD) are the main pharmacologically active compounds of Cannabis sativa. These compounds have, for a long time, been under extensive investigation, and their potent antioxidant and inflammatory properties have been reported, although the detailed mechanisms of their actions have not been fully clarified. CB1 receptors are suggested to be responsible for the analgesic effect of THC, while CB2 receptors may account for its immunomodulatory properties. Unlike THC, CBD has a very low affinity for both CB1 and CB2 receptors, and behaves as their negative allosteric modulator. CBD activity, as a CB2 receptor inverse agonist, could be important for CBD anti-inflammatory properties. In this review, we discuss the chemical properties and bioavailability of THC and CBD, their main mechanisms of action, and their role in oxidative stress and inflammation.”

https://pubmed.ncbi.nlm.nih.gov/35453344/

Anti-Inflammatory and Antiviral Effects of Cannabinoids in Inhibiting and Preventing SARS-CoV-2 Infection

Posted on by
Reply

“The COVID-19 pandemic caused by the SARS-CoV-2 virus made it necessary to search for new options for both causal treatment and mitigation of its symptoms. Scientists and researchers around the world are constantly looking for the best therapeutic options. These difficult circumstances have also spurred the re-examination of the potential of natural substances contained in Cannabis sativa L. Cannabinoids, apart from CB1 and CB2 receptors, may act multifacetedly through a number of other receptors, such as the GPR55, TRPV1, PPARs, 5-HT1A, adenosine and glycine receptors. The complex anti-inflammatory and antiviral effects of cannabinoids have been confirmed by interactions with various signaling pathways. Considering the fact that the SARS-CoV-2 virus causes excessive immune response and triggers an inflammatory cascade, and that cannabinoids have the ability to regulate these processes, it can be assumed that they have potential to be used in the treatment of COVID-19. During the pandemic, there were many publications on the subject of COVID-19, which indicate the potential impact of cannabinoids not only on the course of the disease, but also their role in prevention. It is worth noting that the anti-inflammatory and antiviral potential are shown not only by well-known cannabinoids, such as cannabidiol (CBD), but also secondary cannabinoids, such as cannabigerolic acid (CBGA) and terpenes, emphasizing the role of all of the plant’s compounds and the entourage effect. This article presents a narrative review of the current knowledge in this area available in the PubMed, Scopus and Web of Science medical databases.”

https://pubmed.ncbi.nlm.nih.gov/35456990/

Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies

Posted on by
Reply

“Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference -3.8 mg, 95% CI -10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI -2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.”

https://pubmed.ncbi.nlm.nih.gov/35459926/

In Vitro and In Vivo Anti-Inflammatory Effects of Cannabis sativa Stem Extract

Posted on by
Reply

“With growing scientific interest in cannabinoids, a number of studies have focused on biological activities of cannabidiol and its major source, inflorescence and leaf of Cannabis sativa plant. However, recent analytical chemistry studies have reported the pharmacological significance of non-cannabinoid phytochemicals that are rich in other parts of the plant. Thus, the objective of this study was to investigate the anti-inflammatory effects of Cannabis extracts from plant parts of shelled seeds, roots, and stems containing no or trace amounts of cannabinoids. Among water and ethanol extracts from three plant parts, Cannabis stem ethanol extract (CSE) had the most potent free radical scavenging activities and suppressive effects on the production of nitric oxide from macrophages. In further studies using macrophages, CSE effectively inhibited lipopolysaccharide (LPS)-induced inflammatory responses by suppressing proinflammatory cytokines, nuclear factor-κB and mitogen-activated protein kinase phosphorylations, and cellular accumulation of reactive oxygen species. Moreover, in mice exposed to LPS, CSE reduced tumor necrosis factor-α production and normalized activations of proapoptotic proteins in the liver, kidney, and spleen. Gas chromatography/mass spectrometry analyses of CSE showed several active compounds that might be associated with its antioxidant and anti-inflammatory effects. Collectively, these findings indicate that CSE counteracts LPS-induced acute inflammation and apoptosis, suggesting pharmaceutical applications for the stem part of C. sativa.”

https://pubmed.ncbi.nlm.nih.gov/35438555/

Potential cannabidiol (CBD) repurposing as antibacterial and promising therapy of CBD plus polymyxin B (PB) against PB-resistant gram-negative bacilli

Posted on by
Reply

“This study aimed to assess the ultrapure cannabidiol (CBD) antibacterial activity and to investigate the antibacterial activity of the combination CBD + polymyxin B (PB) against Gram-negative (GN) bacteria, including PB-resistant Gram-negative bacilli (GNB). We used the standard broth microdilution method, checkerboard assay, and time-kill assay. CBD exhibited antibacterial activity against Gram-positive bacteria, lipooligosaccharide (LOS)-expressing GN diplococcus (GND) (Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella catarrhalis), and Mycobacterium tuberculosis, but not against GNB. For most of the GNB studied, our results showed that low concentrations of PB (≤ 2 µg/mL) allow CBD (≤ 4 µg/mL) to exert antibacterial activity against GNB (e.g., Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii), including PB-resistant GNB. CBD + PB also showed additive and/or synergistic effect against LOS-expressing GND. Time-kill assays results showed that the combination CBD + PB leads to a greater reduction in the number of colony forming units per milliliter compared to CBD and PB alone, at the same concentration used in combination, and the combination CBD + PB was synergistic for all four PB-resistant K. pneumoniae isolates evaluated. Our results show that CBD has translational potential and should be further explored as a repurposed antibacterial agent in clinical trials. The antibacterial efficacy of the combination CBD + PB against multidrug-resistant and extensively drug-resistant GNB, especially PB-resistant K. pneumoniae, is particularly promising.”

https://pubmed.ncbi.nlm.nih.gov/35440801/

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

Posted on by
Reply

“Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases for studies reported since 2007 on the use of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in MS and in experimental autoimmune encephalomyelitis (EAE), Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and toxin-induced demyelination models. Study selection and data extraction were performed by 3 reviewers, and 28 studies were selected for inclusion. The certainty of evidence was appraised using the Cochrane GRADE approach. In clinical studies, there was low- and moderate-quality evidence that treatment with ~1:1 CBD/THC mixtures as a nabiximols (Sativex®) oromucosal spray reduced numerical rating scale (NRS) scores for spasticity, pain, and sleep disturbance, diminished bladder overactivity, and decreased proinflammatory cytokine and transcription factor expression levels. Preclinical studies demonstrated decreases in disease severity, hindlimb stiffness, motor function, neuroinflammation, and demyelination. Other experimental systems showed the capacity of cannabinoids to promote remyelination in vitro and by electron microscopy. Modest short-term benefits were realized in MS responders to adjunctive therapy with CBD/THC mixtures. Future studies are recommended to investigate the cellular and molecular mechanisms of cannabinoid effects on MS lesions and to evaluate whether medical marijuana can accelerate remyelination and retard the accrual of disability over the long term.”

https://pubmed.ncbi.nlm.nih.gov/35327341/

Δ 9 -Tetrahydrocannabinol promotes functional remyelination in the mouse brain

Posted on by
Reply

“Background and purpose: Research on demyelinating disorders aims to find novel molecules that are able to induce oligodendrocyte precursor cell differentiation to promote central nervous system remyelination and functional recovery. Δ9 -Tetrahydrocannabinol (THC), the most prominent active constituent of the hemp plant Cannabis sativa, confers neuroprotection in animal models of demyelination. However, the possible effect of THC on myelin repair has never been studied.

Experimental approach: By using oligodendroglia-specific reporter mouse lines in combination with two models of toxin-induced demyelination, we analysed the effect of THC on the processes of oligodendrocyte regeneration and functional remyelination.

Key results: We show that THC administration enhanced oligodendrocyte regeneration, white matter remyelination and motor function recovery. THC also promoted axonal remyelination in organotypic cerebellar cultures. THC remyelinating action relied on the induction of oligodendrocyte precursor differentiation upon cell cycle exit and via CB1 cannabinoid receptor activation.

Conclusions and implications: Overall, our study identifies THC administration as a promising pharmacological strategy aimed to promote functional CNS remyelination in demyelinating disorders.”

https://pubmed.ncbi.nlm.nih.gov/34216154/

The Efficacy of Cannabis in Reducing Back Pain: A Systematic Review

Posted on by
Reply

“Objective: To critically analyze the evidence and efficacy of cannabis to treat surgical and nonsurgical back pain via a Systematic Review.

Methods: We conducted a systematic review to investigate the efficacy of cannabis to treat non-surgical and surgical back pain. A literature search was performed with MEDLINE and Embase databases. Only RCTs and prospective cohort studies with concurrent control were included in this study. Risk of bias and quality grading was assessed for each included study.

Results: Database searches returned 1738 non-duplicated results. An initial screening excluded 1716 results. Twenty-two full text articles were assessed for eligibility. Four articles ultimately met pre-determined eligibility and were included in the study. Two studies addressed post-SCI pain while other two studies addressed low back pain. No studies specifically examined the use of cannabis for surgical back pain. The type of cannabis varied between study and included THC, dronabinol, and Nabilone. A total of 110 patients were included in the four studies reviewed. In each study, there was a quantifiable advantage of cannabis therapy for alleviating back pain. There were no serious adverse effects reported.

Conclusions: In all articles, cannabis was shown to be effective to treat back pain with an acceptable side effect profile. However, long-term follow up is lacking. As medicinal cannabis is being used more commonly for analgesic effect and patients are “self-prescribing” cannabis for back pain, additional studies are needed for healthcare providers to confidently recommend cannabis therapy for back pain.”

https://pubmed.ncbi.nlm.nih.gov/35128969/

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

Posted on by
Reply

“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

Posted on by
Reply

“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/