Tag Archives: THC

Δ9-Tetrahydrocannabinol Prevents Cardiovascular Dysfunction in STZ-Diabetic Wistar-Kyoto Rats.

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“The aim of this study was to determine if chronic, low-dose administration of a nonspecific cannabinoid receptor agonist could provide cardioprotective effects in a model of type I diabetes mellitus.

Δ9-Tetrahydrocannabinol administration to diabetic animals significantly reduced blood glucose concentrations and attenuated pathological changes in serum markers of oxidative stress and lipid peroxidation. Positive changes to biochemical indices in diabetic animals conferred improvements in myocardial and vascular function.

This study demonstrates that chronic, low-dose administration of Δ9-tetrahydrocannabinol can elicit antihyperglycaemic and antioxidant effects in diabetic animals, leading to improvements in end organ function of the cardiovascular system. Implications from this study suggest that cannabinoid receptors may be a potential new target for the treatment of diabetes-induced cardiovascular disease.”   https://www.ncbi.nlm.nih.gov/pubmed/29181404

“The aim of this study was to determine if a nonspecific cannabinoid receptor agonist could provide cardioprotective effects in a model of type I diabetes mellitus. Outcomes from this study indicate that THC administration to STZ improved functional parameters of cardiovascular health by reducing oxidative stress, lipid peroxidation, and blood glucose levels. These results indicate that activation of cannabinoid receptors may be a viable experimental target for the prevention of oxidative stress-induced complications in type I diabetes mellitus.”  https://www.hindawi.com/journals/bmri/2017/7974149/

Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges.

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“It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the “phytocannabinoids” [pCBs; e.g., (-)-trans-Δ9-tetrahydrocannabinol (THC), (-)-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances [“endocannabinoids” (eCB), e.g., arachidonoylethanolamine (anandamide, AEA), 2-arachidonoylglycerol (2-AG), etc.].

These ligands, together with multiple receptors (e.g., CB1 and CB2 cannabinoid receptors, etc.), and a complex enzyme and transporter apparatus involved in the synthesis and degradation of the ligands constitute the endocannabinoid system (ECS), a recently emerging regulator of several physiological processes.

The ECS is widely expressed in the human body, including several members of the innate and adaptive immune system, where eCBs, as well as several pCBs were shown to deeply influence immune functions thereby regulating inflammation, autoimmunity, antitumor, as well as antipathogen immune responses, etc.

Based on this knowledge, many in vitro and in vivo studies aimed at exploiting the putative therapeutic potential of cannabinoid signaling in inflammation-accompanied diseases (e.g., multiple sclerosis) or in organ transplantation, and to dissect the complex immunological effects of medical and “recreational” marijuana consumption.

Thus, the objective of the current article is (i) to summarize the most recent findings of the field; (ii) to highlight the putative therapeutic potential of targeting cannabinoid signaling; (iii) to identify open questions and key challenges; and (iv) to suggest promising future directions for cannabinoid-based drug development.”   https://www.ncbi.nlm.nih.gov/pubmed/29176975

“Although, many open questions await to be answered, pharmacological modulation of the (endo)cannabinoid signaling, and restoration of the homeostatic eCB tone of the tissues augur to be very promising future directions in the management of several pathological inflammation-accompanied diseases.”   https://www.frontiersin.org/articles/10.3389/fimmu.2017.01487/full

Synthesis of Photoswitchable Δ9-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling.

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Journal of the American Chemical Society

“The cannabinoid receptor 1 (CB1) is an inhibitory G protein-coupled receptor abundantly expressed in the central nerv-ous system. It has rich pharmacology and largely accounts for the recreational use of cannabis. We describe efficient asymmetric syntheses of four photoswitchable Δ9-tetrahydrocannabinol derivatives (azo-THCs) from a central building block 3-Br-THC. Using electrophysiology and a FRET-based cAMP assay, two compounds are identified as potent CB1 agonists that change their effect upon illumination. As such, azo-THCs enable CB1-mediated optical control of inwardly-rectifying potassium channels, as well as adenylyl cyclase.”

https://www.ncbi.nlm.nih.gov/pubmed/29161035

http://pubs.acs.org/doi/10.1021/jacs.7b06456

Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings.

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European Journal of Pain

“Cannabinoids have a long record of recreational and medical use and become increasingly approved for pain therapy. This development is based on preclinical and human experimental research summarized in this review.

Cannabinoid CB1 receptors are widely expressed throughout the nociceptive system. Their activation by endogenous or exogenous cannabinoids modulates the release of neurotransmitters. This is reflected in antinociceptive effects of cannabinoids in preclinical models of inflammatory, cancer and neuropathic pain, and by nociceptive hypersensitivity of cannabinoid receptor-deficient mice.

Cannabis-based medications available for humans mainly comprise Δ9 -tetrahydrocannabinol (THC), cannabidiol (CBD) and nabilone.

During the last 10 years, six controlled studies assessing analgesic effects of cannabinoid-based drugs in human experimental settings were reported. An effect on nociceptive processing could be translated to the human setting in functional magnetic resonance imaging studies that pointed at a reduced connectivity within the pain matrix of the brain. However, cannabinoid-based drugs heterogeneously influenced the perception of experimentally induced pain including a reduction in only the affective but not the sensory perception of pain, only moderate analgesic effects, or occasional hyperalgesic effects. This extends to the clinical setting.

While controlled studies showed a lack of robust analgesic effects, cannabis was nearly always associated with analgesia in open-label or retrospective reports, possibly indicating an effect on well-being or mood, rather than on sensory pain. Thus, while preclinical evidence supports cannabinoid-based analgesics, human evidence presently provides only reluctant support for a broad clinical use of cannabinoid-based medications in pain therapy.

SIGNIFICANCE:

Cannabinoids consistently produced antinociceptive effects in preclinical models, whereas they heterogeneously influenced the perception of experimentally induced pain in humans and did not provide robust clinical analgesia, which jeopardizes the translation of preclinical research on cannabinoid-mediated antinociception into the human setting.”

https://www.ncbi.nlm.nih.gov/pubmed/29160600

http://onlinelibrary.wiley.com/doi/10.1002/ejp.1148/abstract?systemMessage=Wiley+Online+Library+usage+report+download+page+will+be+unavailable+on+Friday+24th+November+2017+at+21%3A00+EST+%2F+02.00+GMT+%2F+10%3A00+SGT+%28Saturday+25th+Nov+for+SGT+

Effects of chronic Δ9-tetrahydrocannabinol treatment on Rho/Rho-kinase signalization pathway in mouse brain.

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Saudi Pharmaceutical Journal

“Δ9-Tetrahydrocannabinol (Δ9-THC) shows its effects by activating cannabinoid receptors which are on some tissues and neurons. Cannabinoid systems have role on cell proliferation and development of neurons. Furthermore, it is interesting that cannabinoidsystem and rho/rho-kinase signalization pathway, which have important role on cell development and proliferation, may have role on neuron proliferation and development together. Thus, a study is planned to investigate rhoA and rho-kinase enzyme expressions and their activities in the brain of chronic Δ9-THC treated mice. One group of mice are treated with Δ9-THC once to see effects of acute treatment. Another group of mice are treated with Δ9-THC three times per day for one month. After this period, rhoA and rho-kinase enzyme expressions and their activities in mice brains are analyzed by ELISA method. Chronic administration of Δ9-THC decreased the expression of rhoA while acute treatment has no meaningful effect on it. Administration of Δ9-THC did not affect expression of rho-kinase on both chronic and acute treatment. Administration of Δ9-THC increased rho-kinase activity on both chronic and acute treatment, however, chronic treatment decreased its activity with respect to acute treatment. This study showed that chronic Δ9-THC treatment down-regulated rhoA expression and did not change the expression level of rho-kinase which is downstream effector of rhoA. However, it elevated the rho-kinase activity. Δ9-THC induced down-regulation of rhoA may cause elevation of cypin expression and may have benefit on cypin related diseases. Furthermore, use of rho-kinase inhibitors and Δ9-THC together can be useful on rho-kinase related diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/29158718
http://www.sciencedirect.com/science/article/pii/S1319016417301081?via%3Dihub

Multiple sclerosis symptoms and spasticity management: new data.

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Future Medicine Logo

“Spasticity, perceived by patients as muscle rigidity and spasms, is a common symptom in multiple sclerosis (MS). It is associated with functional impairment that can exacerbate other MS symptoms and reduce quality of life.

Pharmacological treatment options are limited and frequently ineffective. Treatment adherence is a key issue to address in these patients.

The efficacy and safety of 9-delta-tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray for treatment of MS spasticity were demonstrated in four Phase III trials.

Observational studies and registry data subsequently confirmed the effectiveness and tolerability of THC:CBD oromucosal spray under everyday practice conditions.

Among patients who respond to treatment, THC:CBD oromucosal spray has been shown to produce positive improvements in gait parameters and to normalize muscle fibers.”

https://www.ncbi.nlm.nih.gov/pubmed/29143581
https://www.futuremedicine.com/doi/10.2217/nmt-2017-0034

Medical cannabis Q&A

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  • “1. What is medical cannabis?

The term “medical cannabis” is used to describe products derived from the whole cannabis plant or its extracts containing a variety of active cannabinoids and terpenes, which patients take for medical reasons, after interacting with and obtaining authorization from their health care practitioner.

  • 2. What are the main active ingredients?

The chemical ingredients of cannabis are called cannabinoids. The 2 main therapeutic ones are:

  •  A Tetrahydrocannabinol (THC) is a partial agonist of CB1 and CB2 receptors. It is psychoactive and produces the euphoric effect.
  •  B Cannabidiol (CBD) has a weak affinity for CB1 and CB2 receptors and appears to exert its activity by enhancing the positive effects of the body’s endogenous cannabinoids
 3. Why do patients take it?

Medical cannabis may be used to alleviate symptoms for a variety of conditions. It has most commonly been used in neuropathic pain and other chronic pain conditions. There is limited, but developing, clinical evidence surrounding its safety and efficacy, and it does not currently have an approved Health Canada indication.

  • 4. How do patients take it?

Cannabis can be smoked, vaporized, taken orally, sublingually, topically or rectally. Different routes of administration will result in different pharmacokinetic and pharmacodynamic properties of the drug.

  • 5. Is it possible to develop dependence on medical cannabis?

Yes, abrupt discontinuation after long-term use may result in withdrawal symptoms. Additionally, chronic use may result in psychological dependence.

  • 6. What is the difference between medical and recreational cannabis?

Patients taking cannabis for medical reasons generally use cannabinoids to alleviate symptoms while minimizing intoxication, whereas recreational users may be taking cannabis for euphoric effects. Medical cannabis is authorized by a prescriber who provides a medical document allowing individuals to obtain cannabis from a licensed producer or apply to Health Canada to grow their own, whereas recreational cannabis is currently obtained through illicit means.

  • 7. How can patients access cannabis for medical purposes?
  • 8. Does medical cannabis have a DIN?

Pharmacological cannabinoids such as Sativex (delta-9-tetrahydrocannabinol-cannabidiol) and Cesamet (nabilone) have been approved for specific indications by Health Canada, however, herbal medical cannabis has not gone through Health Canada’s drug review and approval process, nor does it have a Drug Identification Number (DIN) or Natural Product Number (NPN).

  • 9. Is medical cannabis covered through insurance?

Some insurance plans may cover medical cannabis. Check each patient’s individual plan for more details.

  • 10. What role can pharmacists play in medical cannabis?

Even though pharmacists are not dispensing medical cannabis at this time, it is important for them to understand how their patients may use and access medical cannabis in order to provide effective medication management. Pharmacists may provide counselling on areas such as contraindications, drug interactions, management of side effects, alternative therapies, potential addictive behaviour and appropriate use.

  • 11. Where can I find more information about medical cannabis?

You can find more information on Health Canada’s website:” https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-use-marijuana/medical-use-marijuana.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661684/

Availability and approval of cannabis-based medicines for chronic pain management and palliative/supportive care in Europe: A survey of the status in the chapters of the European Pain Federation.

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European Journal of Pain

“There is considerable public and political interest in the use of cannabis products for medical purposes.

METHODS:

The task force of the European Pain Federation (EFIC) conducted a survey with its national chapters representatives on the status of approval of all types of cannabis-based medicines, the covering of costs and the availability of a position paper of a national medical association on the use of medical cannabis for chronic pain and for symptom control in palliative/supportive care.

RESULTS:

Thirty-one out of 37 contacted councillors responded. Plant-derived tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray is approved for spasticity in multiple sclerosis refractory to conventional treatment in 21 EFIC chapters. Plant-derived THC (dronabinol) is approved for some palliative care conditions in four EFIC chapters. Synthetic THC analogue (nabilone) is approved for chemotherapy-associated nausea and vomiting refractory to conventional treatment in four EFIC chapters’. Eight EFIC chapters’ countries have an exceptional and six chapters an expanded access programme for medical cannabis. German and Israeli pain societies recommend the use of cannabis-based medicines as third-line drug therapies for chronic pain within a multicomponent approach. Conversely, the German medical association and a team of finish experts and officials do not recommend the prescription of medical cannabis due to the lack of high-quality evidence of efficacy and the potential harms.

CONCLUSIONS:

There are marked differences between the countries represented in EFIC in the approval and availability of cannabis-based products for medical use. EFIC countries are encouraged to collaborate with the European Medicines Agency to publish a common document on cannabis-based medicines.

SIGNIFICANCE:

There are striking differences between European countries in the availability of plant-derived and synthetic cannabinoids and of medical cannabis for pain management and for symptom control in palliative care and in the covering of costs by health insurance companies or state social security systems.”

https://www.ncbi.nlm.nih.gov/pubmed/29134767

http://onlinelibrary.wiley.com/doi/10.1002/ejp.1147/abstract

Involvement of cannabinoid receptor type 2 in light-induced degeneration of cells from mouse retinal cell line in vitro and mouse photoreceptors in vivo.

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Experimental Eye Research

“Earlier studies showed that the expressions of the agonists of the cannabinoid receptors are reduced in the vitreous humor of patients with age-related macular degeneration (AMD), and the cannabinoid type 2 receptor is present in the retinas of rats and monkeys. The purpose of this study was to determine whether the cannabinoid type 2 receptor is involved in the light-induced death of cultured 661W cells, an immortalized murine retinal cell line, and in the light-induced retinal degeneration in mice.

Time-dependent changes in the expression and location of retinal cannabinoid type 2 receptor were determined by Western blot and immunostaining. The cannabinoid type 2 receptor was down-regulated in murine retinae and cone cells. In the in vitro studies, HU-308, a cannabinoidtype 2 receptor agonist, had a protective effect on the light-induced death of 661W cells, and this effect was attenuated by SR144528, a cannabinoid type 2 receptor antagonist.

Because the cannabinoid type 2 receptor is a G-protein coupled receptor and is coupled with Gi/o protein, we investigated the effects of the cAMP-dependent protein kinase (PKA). HU-308 and H89, a PKA inhibitor, deactivated PKA in retinal cone cells, and H89 also suppressed light-induced cell death. For the in vivo studies, a cannabinoid type 2 receptor agonist, HU-308, or an antagonist, SR144528, was injected intravitreally into mouse eyes before the light exposure. Electroretinography was used to determine the physiological status of the retinas. Injection of HU-308 improved the a- and b-waves of the ERGs and also the thickness of the outer nuclear layer of the murine retina after light exposure.

These findings indicate that the cannabinoid type 2 receptor is involved in the light-induced retinal damage through PKA signaling. Thus, activation of cannabinoidtype 2 receptor may be a therapeutic approach for light-associated retinal diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/29133122

http://www.sciencedirect.com/science/article/pii/S0014483516304456?via%3Dihub

Pharmacokinetic and behavioural profile of THC, CBD, and THC+CBD combination after pulmonary, oral, and subcutaneous administration in rats and confirmation of conversion in vivo of CBD to THC.

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European Neuropsychopharmacology Home

“Of central importance was the novel finding that THC can be detected in serum and brain after administration of CBD alone which, if confirmed in humans and given the increasing medical use of CBD-only products, might have important legal and forensic ramifications.” https://www.ncbi.nlm.nih.gov/pubmed/29129557  http://www.europeanneuropsychopharmacology.com/article/S0924-977X(17)30983-5/fulltext