Category Archives: THC (Delta-9-Tetrahydrocannabinol)

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

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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

Perceived Efficacy of Medical Cannabis in the Treatment of Co-Occurring Health-Related Quality of Life Symptoms.

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 Publication Cover“For persons living with chronic conditions, health-related quality of life (HRQoL) symptoms, such as pain, anxiety, depression, and insomnia, often interact and mutually reinforce one another.

There is evidence that medical cannabis (MC) may be efficacious in ameliorating such symptoms and improving HRQoL.

As many of these HRQoL symptoms may mutually reinforce one another, we conducted an exploratory study to investigate how MC users perceive the efficacy of MC in addressing co-occurring HRQoL symptoms. We conducted a cross-sectional online survey of persons with a state medical marijuana card in Illinois (N = 367) recruited from licensed MC dispensaries across the state. We conducted tests of ANOVA to measure how perceived MC efficacy for each HRQoL symptom varied by total number of treated symptoms reported by participants.

Pain was the most frequently reported HRQoL treated by MC, followed by anxiety, insomnia, and depression. A large majority of our sample (75%) reported treating two or more HRQoL symptoms. In general, perceived efficacy of MC in relieving each HRQoL symptom category increased with the number of co-occurring symptoms also treated with MC. Perceived efficacy of MC in relieving pain, anxiety, and depression varied significantly by number of total symptoms experienced.

This exploratory study contributes to our understanding of how persons living with chronic conditions perceive the efficacy of MC in treating co-occurring HRQoL symptoms. Our results suggest that co-occurring pain, anxiety, and depression may be particularly amenable to treatment with MC.”

https://www.ncbi.nlm.nih.gov/pubmed/31693457

https://www.tandfonline.com/doi/abs/10.1080/08964289.2019.1683712?journalCode=vbmd20

Targeting the cannabinoid receptor CB2 in a mouse model of l-dopa induced dyskinesia.

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Neurobiology of Disease“L-dopa induced dyskinesia (LID) is a debilitating side-effect of the primary treatment used in Parkinson’s disease (PD), l-dopa. Here we investigate the effect of HU-308, a cannabinoid CB2 receptor agonist, on LIDs.

Utilizing a mouse model of PD and LIDs, induced by 6-OHDA and subsequent l-dopa treatment, we show that HU-308 reduced LIDs as effectively as amantadine, the current frontline treatment. Furthermore, treatment with HU-308 plus amantadine resulted in a greater anti-dyskinetic effect than maximally achieved with HU-308 alone, potentially suggesting a synergistic effect of these two treatments. Lastly, we demonstrated that treatment with HU-308 and amantadine either alone, or in combination, decreased striatal neuroinflammation, a mechanism which has been suggested to contribute to LIDs.

Taken together, our results suggest pharmacological treatments with CB2 agonists merit further investigation as therapies for LIDs in PD patients. Furthermore, since CB2 receptors are thought to be primarily expressed on, and signal through, glia, our data provide weight to suggestion that neuroinflammation, or more specifically, altered glial function, plays a role in development of LIDs.”

https://www.ncbi.nlm.nih.gov/pubmed/31669673

“Collectively, our findings suggest CB2 agonists offer a putative target to treat LIDs, with efficacy comparable to the frontline treatment amantadine. Our study suggests that targeting glial function may be an important strategy for developing therapies for treating LIDs, a major unmet need for PD patients.”

https://www.sciencedirect.com/science/article/pii/S0969996119303213?via%3Dihub

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

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 “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

Structure of an allosteric modulator bound to the CB1 cannabinoid receptor.

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Image result for nature chemical biology“The CB1 receptor mediates the central nervous system response to cannabinoids, and is a drug target for pain, anxiety and seizures.

CB1 also responds to allosteric modulators, which influence cannabinoid binding and efficacy.

To understand the mechanism of these compounds, we solved the crystal structure of CB1 with the negative allosteric modulator (NAM) ORG27569 and the agonist CP55940.

The structure reveals that the NAM binds to an extrahelical site within the inner leaflet of the membrane, which overlaps with a conserved site of cholesterol interaction in many G protein-coupled receptors (GPCRs).

The ternary structure with ORG27569 and CP55940 captures an intermediate state of the receptor, in which aromatic residues at the base of the agonist-binding pocket adopt an inactive conformation despite the large contraction of the orthosteric pocket.

The structure illustrates a potential strategy for drug modulation of CB1 and other class A GPCRs.”

https://www.ncbi.nlm.nih.gov/pubmed/31659318

https://www.nature.com/articles/s41589-019-0387-2

Cannabinoid receptor 2‑selective agonist JWH015 attenuates bone cancer pain through the amelioration of impaired autophagy flux induced by inflammatory mediators in the spinal cord.

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Journal Cover “Bone cancer pain (BCP) is a severe complication of advanced bone cancer.

Although cannabinoid receptor 2 (CB2) agonists may have an analgesic effect, the underlying mechanism remains unclear.

CB2 serves a protective role in various pathological states through the activation of autophagy. Therefore, the present study aimed to determine whether the analgesic effects of the selective CB2 agonist JWH015 was mediated by the activation of autophagy in BCP.

The results of the present study suggested that the impairment of autophagy flux was induced by glia‑derived inflammatory mediators in spinal neurons. Intrathecal administration of the selective CB2 agonist JWH015 ameliorated autophagy flux through the downregulation of IL‑1β and IL‑6 and attenuated BCP.”

https://www.ncbi.nlm.nih.gov/pubmed/31661120

https://www.spandidos-publications.com/10.3892/mmr.2019.10772

WIN55,212-2-Induced Expression of Mir-29b1 Favours the Suppression of Osteosarcoma Cell Migration in a SPARC-Independent Manner.

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ijms-logo“WIN55,212-2 (WIN) is a synthetic agonist of cannabinoid receptors that displays promising antitumour properties.

The aim of this study is to demonstrate that WIN is able to block the migratory ability of osteosarcoma cells and characterize the mechanisms involved.

Overall, these findings suggest that WIN markedly affects cell migration, dependently on miR-29b1 and independently of SPARC, and can thus be considered as a potential innovative therapeutic agent in the treatment of osteosarcoma.”

https://www.ncbi.nlm.nih.gov/pubmed/31652569

https://www.mdpi.com/1422-0067/20/20/5235

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

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“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.

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 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

Medical Cannabis for the Primary Care Physician.

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 SAGE Journals“Medical cannabis use is common in the United States and increasingly more socially acceptable. As more patients seek out and acquire medical cannabis, primary care physicians will be faced with a growing number of patients seeking information on the indications, efficacy, and safety of medical cannabis. We present a case of a patient with several chronic health conditions who asks her primary care provider whether she should try medical cannabis. We provide a review of the pharmacology of medical cannabis, the state of evidence regarding the efficacy of medical cannabis, variations in the types of medical cannabis, and safety monitoring considerations for the primary care physician.”

https://www.ncbi.nlm.nih.gov/pubmed/31646929

https://journals.sagepub.com/doi/10.1177/2150132719884838