Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Opioid-Sparing Effects of Cannabinoids on Morphine Analgesia: Participation of CB1 and CB2 Receptors.

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British Journal of Pharmacology banner“Much of the opioid epidemic arose from abuse of prescription opioid drugs.

This study sought to determine if the combination of a cannabinoid with an opioid could produce additive or synergistic effects on pain, allowing reduction in the opioid dose needed for maximal analgesia.

CONCLUSIONS AND IMPLICATIONS:

The ability of a cannabinoid to produce an additive or synergistic effect on analgesia when combined with morphine varies with the pain assay and may be mediated by CB1 or CB2 receptors. These results hold the promise of using cannabinoids to reduce the dose of opioids for analgesia in certain pain conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31218677

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14769

Therapeutic impact of orally administered cannabinoid oil extracts in an experimental autoimmune encephalomyelitis animal model of multiple sclerosis.

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Biochemical and Biophysical Research Communications“There is a growing surge of investigative research involving the beneficial use of cannabinoids as novel interventional alternatives for multiple sclerosis (MS) and associated neuropathic pain (NPP).

Using an experimental autoimmune encephalomyelitis (EAE) animal model of MS, we demonstrate the therapeutic effectiveness of two cannabinoid oil extract formulations (10:10 & 1:20 – tetrahydrocannabinol/cannabidiol) treatment.

Our research findings confirm that cannabinoid treatment produces significant improvements in neurological disability scoring and behavioral assessments of NPP that directly result from their ability to reduce tumor necrosis factor alpha (TNF-α) production and enhance brain derived neurotrophic factor (BDNF) production.

Henceforth, this research represents a critical step in advancing the literature by scientifically validating the merit for medical cannabinoid use and sets the foundation for future clinical trials.”

https://www.ncbi.nlm.nih.gov/pubmed/31213295

“Cannabinoid treatment produces improvements in neurological disability scoring. Cannabinoid treatment also improves behavioral assessments of neuropathic pain.”

https://www.sciencedirect.com/science/article/pii/S0006291X19311568?via%3Dihub

The origins of cannabis smoking: Chemical residue evidence from the first millennium BCE in the Pamirs.

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 Science Advances: 5 (6)“Cannabis is one of the oldest cultivated plants in East Asia, grown for grain and fiber as well as for recreational, medical, and ritual purposes. It is one of the most widely used psychoactive drugs in the world today, but little is known about its early psychoactive use or when plants under cultivation evolved the phenotypical trait of increased specialized compound production. The archaeological evidence for ritualized consumption of cannabis is limited and contentious. Here, we present some of the earliest directly dated and scientifically verified evidence for ritual cannabis smoking. This phytochemical analysis indicates that cannabis plants were burned in wooden braziers during mortuary ceremonies at the Jirzankal Cemetery (ca. 500 BCE) in the eastern Pamirs region. This suggests cannabis was smoked as part of ritual and/or religious activities in western China by at least 2500 years ago and that the cannabis plants produced high levels of psychoactive compounds.”

https://www.ncbi.nlm.nih.gov/pubmed/31206023

https://advances.sciencemag.org/content/5/6/eaaw1391

“Earliest evidence for cannabis smoking discovered in ancient tombs”  https://www.nationalgeographic.com/culture/2019/06/earliest-evidence-cannabis-marijuana-smoking-china-tombs/

“The First Evidence of Smoking Pot Was Found in a 2,500-Year-Old Pot”  https://www.smithsonianmag.com/smart-news/2500-year-old-chinese-cemetery-offers-earliest-physical-evidence-cannabis-smoking-180972410/

“Earliest Evidence of People “Smoking” Weed Found in 2,500-Year-Old Chinese Pots”  https://www.sciencealert.com/ancient-pots-from-china-reveal-humans-smoking-cannabis-2-500-years-ago

“Oldest evidence of marijuana use discovered in 2500-year-old cemetery in peaks of western China” https://www.sciencemag.org/news/2019/06/oldest-evidence-marijuana-use-discovered-2500-year-old-cemetery-peaks-western-china

“Cannabis use for medicinal purposes dates back at least 3,000 years.”  https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_7

“Cannabis has been used for medicinal purposes for thousands of years.” https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq

“The use of Cannabis for medicinal purposes dates back to ancient times.” http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq#section/all

Safety and effectiveness of cannabinoids for the treatment of neuropsychiatric symptoms in dementia: a systematic review.

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SAGE Journals“Neuropsychiatric symptoms (NPS) in dementia impact profoundly on the quality of life of people living with dementia and their care givers. Evidence for the effectiveness and safety of current therapeutic options is varied.

Cannabinoids have been proposed as an alternative therapy, mainly due to their activity on CB1 receptors in the central nervous system. However, little is known regarding the safety and effectiveness of cannabinoid therapy in people with dementia.

A literature review was undertaken to identify, describe and critically appraise studies investigating cannabinoid use in treating NPS in dementia.

RESULTS:

Twelve studies met the inclusion criteria. There was considerable variability across the studies with respect to study design (50% randomized controlled trials), intervention [dronabinol (33%), nabilone (25%) or delta-9 tetrahydrocannabinol (THC; 42%)] and outcome measures.

Dronabinol (three studies) and THC (one study) were associated with significant improvements in a range of neuropsychiatric scores.

The most common adverse drug event (ADE) reported was sedation. A high risk of bias was found in eight studies. The highest-quality trial found no significant improvement in symptoms or difference in ADE rate between treatment arms. Included studies used low doses of oral cannabinoids and this may have contributed to the lack of demonstrated efficacy.

CONCLUSION:

While the efficacy of cannabinoids was not proven in a robust randomized control trial, observational studies showed promising results, especially for patients whose symptoms were refractory. In addition, the safety profile is favourable as most of the ADEs reported were mild. Future trials may want to consider dose escalation and formulations with improved bioavailability.”

https://www.ncbi.nlm.nih.gov/pubmed/31205674

https://journals.sagepub.com/doi/10.1177/2042098619846993

Endogenous and synthetic cannabinoids induce the downregulation of cannabinoid CB1 receptor in retina.

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Experimental Eye Research

“Endogenous and synthetic cannabinoids have been shown to provide neuroprotection to retinal neurons in acute animal models of retinopathy.

Chronic exposure to cannabinoid receptor (CB1R) agonists has been reported to induce downregulation of the CB1R in brain and behavioral tolerance.

The aim of this study was to investigate the effect of subchronic/chronic cannabinoid administration on CB1R downregulation in normal rat retina, its downstream prosurvival signaling and subsequent effect on retinal neuroprotection against AMPA excitotoxicity.

This study provides novel information regarding agonist-induced CB1R downregulation in rat retina after subchronic/chronic cannabinoid treatment, and its effect on downstream prosurvival signaling and neuroprotection.”

https://www.ncbi.nlm.nih.gov/pubmed/31199905

https://www.sciencedirect.com/science/article/pii/S0014483519301216?via%3Dihub

Cannabis treatment in hospitalized patients using the SYQE inhaler: Results of a pilot open-label study.

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“The objectives were to evaluate the, usability, feasibility of use, satisfaction, and safety of the Syqe Inhaler Exo (Syqe Inhaler), a metered dose, Pharmacokinetics-validated, cannabis inhaler device in a cohort of hospitalized patients that were using medical cannabis under license as a part of their ongoing medical treatment.

Before and after inhaling from the Syqe Inhaler, participants were asked to fill a questionnaire regarding pain reduction on a visual analog scale from 0 to 10 and, if relevant, reduction in chemotherapy-induced nausea and vomiting and/or spasticity. A patient satisfaction questionnaire and a usability questionnaire were filled in following the last use. Prescribed treatment included 4 daily doses of 500 μg tetrahydrocannabinol each delivered from 16 mg cannabis flos per inhalation plus up to an additional four SOS (distress code for more doses of cannabis) doses.

Result: Daily cannabis dose consumed during hospitalization with the Syqe Inhaler was 51 mg (20-96) versus 1,000 mg (660-3,300) consumed prehospitalization. Patients were easily trained and continued to use Syqe Inhaler for the duration of their hospitalization (5 [3-7] days).

Pain intensity 30-60 minutes following inhalations was reported to be significantly lower than preinhalation 4 [1-5] versus 7 [2-9]). Participants ranked their satisfaction with Syqe Inhaler as 6 (5-7). Three participants reported mild cough, which resolved spontaneously.

Significance of results: Cannabis inhalation by combustion is not feasible for hospitalized patients. The use of Syqe Inhaler during hospitalization yielded high levels of patients and staff satisfaction with no complications.”

https://www.ncbi.nlm.nih.gov/pubmed/31196236

https://www.cambridge.org/core/journals/palliative-and-supportive-care/article/cannabis-treatment-in-hospitalized-patients-using-the-syqe-inhaler-results-of-a-pilot-openlabel-study/0C1940413E704A7EADCB949F5F49603A

Effectiveness and tolerability of THC:CBD oromucosal spray as add-on measure in patients with severe chronic pain: analysis of 12-week open-label real-world data provided by the German Pain e-Registry.

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Image result for J Pain Res.

“Objective: To evaluate effectiveness, tolerability and safety of an oromucosal spray containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as add-on treatment in patients with severe chronic pain (SCP).

Conclusion: THC:CBD oromucosal spray proved to be an effective and well-tolerated add-on treatment for patients with elsewhere refractory chronic pain – especially of neuropathic origin.”

 https://www.ncbi.nlm.nih.gov/pubmed/31190969
https://www.dovepress.com/effectiveness-and-tolerability-of-thccbd-oromucosal-spray-as-add-on-me-peer-reviewed-article-JPR

Selective modulation of the cannabinoid type 1 (CB1) receptor as an emerging platform for the treatment of neuropathic pain.

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“Neuropathic pain is caused by a lesion or dysfunction in the nervous system, and it may arise from illness, be drug-induced or caused by toxin exposure. Since the discovery of two G-protein-coupled cannabinoid receptors (CB1 and CB2) nearly three decades ago, there has been a rapid expansion in our understanding of cannabinoid pharmacology. This is currently one of the most active fields of neuropharmacology, and interest has emerged in developing cannabinoids and other small molecule modulators of CB1 and CB2 as therapeutics for neuropathic pain. This short review article provides an overview of the chemotypes currently under investigation for the development of novel neuropathic pain treatments targeting CB1 receptors.”

 https://www.ncbi.nlm.nih.gov/pubmed/31191856
https://pubs.rsc.org/en/content/articlelanding/2019/MD/C8MD00595H#!divAbstract
Graphical abstract: Selective modulation of the cannabinoid type 1 (CB1) receptor as an emerging platform for the treatment of neuropathic pain

[Cannabis for medical purposes and its prescription].

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“Since 10 March 2017, physicians have been allowed to prescribe cannabis to patients with serious illnesses and in the absence of alternative therapies. Patients can obtain it as dried flowers or extracts in standardised pharmaceutical quality by prescription (narcotic prescription, except for cannabidiol) in pharmacies. When prescribing, physicians have to take a few things into account. The first step is to decide which therapeutic effects are to be achieved and which is the most suitable cannabis product. Cannabis for medical use must meet the requirements for pharmaceutical quality. An identity check must be carried out in the pharmacy on the basis of the monographs of the German Pharmacopoeia (DAB) or the German Pharmaceutical Codex/New Prescription Form (DAC/NRF). For the production of prescription drugs, e.g. capsules, drops or inhalates, there are also corresponding monographs for the preparation of prescription drugs. These standardised, quality-assured prescription formulas should be given preference in the case of a medical prescription. When prescribing an oral or inhalative form of application, it should be noted that the onset and duration of action are very different. Also, due to the complex pharmacology of cannabinoids, interindividual genetic differences in the metabolisation of ∆9-tetrahydrocannabinol (THC), the individual structure and function of the cannabinoid receptors, as well as differences in receptor density and distribution, the dosage and frequency of application must be individually determined. Last but not least, the dosage also depends on the type of disease and individual susceptibility to side effects. When prescribed for the first time, a creeping dosage with a very low initial dose is recommended.”

https://www.ncbi.nlm.nih.gov/pubmed/31187182

https://link.springer.com/article/10.1007%2Fs00103-019-02970-6

Availability of legalized cannabis reduces demand for illegal cannabis among Canadian cannabis users: evidence from a behavioural economic substitution paradigm.

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“In the context of cannabis legalization, an important question among clinicians, policymakers, and the public is whether availability of legal cannabis will significantly reduce consumption (demand) of illegal cannabis.

Using paradigms from behavioural economics, we tested the prediction that legal cannabis would be an asymmetrical substitute for illegal cannabis, with legal cannabis operating as a superior commodity based on its regulated status. In a sample of 289 adult cannabis users in Ontario, we found evidence of substitutability for both legal and illegal cannabis, but significantly lower substitutability of illegal for legal cannabis, a pattern that was also present for price elasticity (α) and Pmax.

Thus, the data indicated asymmetric substitution such that the availability of legal cannabis substantially decreased demand for illegal cannabis, but a significantly smaller effect in reverse.

These results suggest that the introduction of legal cannabis into the market may disrupt and reduce illegal purchases, contributing to the reduction of the potential harms associated with the illegal market.

However, in revealing price windows in which legal cannabis is preferred over the contraband alternative, these data also have significant implications for pricing policies.”

https://www.ncbi.nlm.nih.gov/pubmed/30523535

https://link.springer.com/article/10.17269%2Fs41997-018-0160-4