Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Cannabinoids, inflammation, and fibrosis.

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“Cannabinoids apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs).

As a class, the cannabinoids are generally free from the adverse effects associated with NSAIDs. Their clinical development thus provides a new approach to treatment of diseases characterized by acute and chronic inflammation and fibrosis.

A concise survey of the anti-inflammatory actions of the phytocannabinoids Δ9-tetrahydrocannabinol (THC), cannabidiol, cannabichromene, and cannabinol is presented.

Mention is also made of the noncannabinoid plant components and pyrolysis products, followed by a discussion of 3 synthetic preparations-Cesamet (nabilone; Meda Pharmaceuticals, Somerset, NJ, USA), Marinol (THC; AbbVie, Inc., North Chicago, IL, USA), and Sativex (Cannabis extract; GW Pharmaceuticals, Cambridge United Kingdom)-that have anti-inflammatory effects. A fourth synthetic cannabinoid, ajulemic acid (CT-3, AJA; Resunab; Corbus Pharmaceuticals, Norwood, MA, USA), is discussed in greater detail because it represents the most recent advance in this area and is currently undergoing 3 phase 2 clinical trials by Corbus Pharmaceuticals.

The endogenous cannabinoids, including the closely related lipoamino acids, are then discussed. The review concludes with a presentation of a possible mechanism for the anti-inflammatory and antifibrotic actions of these substances.

Thus, several cannabinoids may be considered candidates for development as anti-inflammatory and antifibrotic agents. Of special interest is their possible use for treatment of chronic inflammation, a major unmet medical need.”

http://www.ncbi.nlm.nih.gov/pubmed/27435265

Cannabinoid receptor agonist WIN55,212-2 and fatty acid amide hydrolase inhibitor URB597 may protect against cognitive impairment in rats of chronic cerebral hypoperfusion via PI3K/AKT signaling.

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“The present study further investigated the protective effects of cannabinoid receptor agonist WIN55,212-2 (WIN) and fatty acid amide hydrolase (FAAH) inhibitor URB597 (URB) on chronic cerebral hypoperfusion (CCH)-induced cognitive impairment in rats.

These findings suggest that WIN and URB are promising agents for therapeutic management of CCH.”

http://www.ncbi.nlm.nih.gov/pubmed/27424778

“Chronic cerebral hypoperfusion (CCH) is one of the causes of vascular dementia (VaD) and is also an etiological factor for Alzheimer’s disease (AD).”  http://journal.frontiersin.org/article/10.3389/fnagi.2014.00010/full

Evaluation of Δ(9)-tetrahydrocannabinol metabolites and oxidative stress in type 2 diabetic rats.

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“Cannabis has been known to be the oldest psychoactive plant for years. It is classified in the Cannabis genus, which is part of the Cannabacea family.

Cannabis sativa L. is the most common species. Δ9-tetrahydrocannabinol (THC) is the main psychoactive constituent identified in Cannabis sativa L.

THC is the most notable cannabinoid among all phytocannabinoids.

THC is exposed to degradation and converted into its active and inactive metabolites that are conjugated with glucuronic acid, and excreted in urine. THC is converted to active metabolite, 11-hydroxy-Δ9-THC (11-OH-THC), and then converted to an inactive metabolite, 11-nor-9-carboxy- Δ9-THC (THC – COOH).

ElSohly and Slade mention that C. sativa and its products have been used as medicinal agents.

Cannabinoids show a variety of therapeutic effects against chronic pain and muscle spasms, nausea and anorexia caused by HIV treatment, vomiting and nausea caused by cancer chemotherapy as well as anorexia associated with weight loss caused by immune deficiency syndrome.

Many studies report that THC provides protection against neuronal injury in a cell culture model of Parkinson disease and experimental models of Huntington disease, exhibits anti-oxidative action and mitigates the severity of the autoimmune response in an experimental model of diabetes.

The development and progression of diabetes mellitus and its complications arise out of increased oxidative damage. Kassab and Piwowar report that the best-known pathways of diabetic complications include oxidative stress.

The aims of the study presented in this paper were: (a) to explain the effects of THC on oxidative stress in T2DM treated with THC and (b) to determine the level of THC metabolites in the urine of diabetic and control rats induced by THC injection.

The object of the study is to examine the effects of Δ(9)-tetrahydrocannabinol (THC) against oxidative stress in the blood and excretion of THC metabolites in urine of type 2 diabetic rats.

These findings highlight that THC treatment may attenuate slightly the oxidative stress in diabetic rats.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818362/

Cannabinoids protect cells from oxidative cell death: a receptor-independent mechanism.

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Journal of Pharmacology and Experimental Therapeutics

“Serum is required for the survival and growth of most animal cells. In serum-free medium, B lymphoblastoid cells and fibroblasts die after 2 days.

We report that submicromolar concentrations of Delta(9)-tetrahydrocannabinol (THC), Delta(8)-THC, cannabinol, or cannabidiol, but not WIN 55,212-2, prevented serum-deprived cell death. Delta(9)-THC also synergized with platelet-derived growth factor in activating resting NIH 3T3 fibroblasts.

The cannabinoids‘ growth supportive effect did not correlate with their ability to bind to known cannabinoid receptors and showed no stereoselectivity, suggesting a nonreceptor-mediated pathway.

Direct measurement of oxidative stress revealed that cannabinoids prevented serum-deprived cell death by antioxidation.

The antioxidative property of cannabinoids was confirmed by their ability to antagonize oxidative stress and consequent cell death induced by the retinoid anhydroretinol.

Therefore, cannabinoids act as antioxidants to modulate cell survival and growth of B lymphocytes and fibroblasts.”

http://www.ncbi.nlm.nih.gov/pubmed/10869379/

“Marijuana has been known for centuries to be a psychoactive medicinal plant. Cannabinoids, especially the nonpsychoactive cannabinoids, may become clinically useful antioxidants in preventing and treating the oxidative stress-related diseases.” http://jpet.aspetjournals.org/content/293/3/807.long

Δ9-tetrahydrocannabinol treatment improved endothelium-dependent relaxation on streptozotocin/nicotinamide-induced diabetic rat aorta.

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“In this study, we investigated the possible effect of Δ(9)-tetrahydrocannabinol (THC), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, on metabolic control and vascular complications of diabetes in streptozotocin/nicotinamide (STZ/NIC) induced type 2 diabetes mellitus.

These results suggested that THC improved endothelium-dependent relaxation in STZ/NIC induced diabetic rat aorta and that these effects were mediated at least in part, by control of hyperglycemia and enhanced endothelial nitric oxide bioavailability.”

Biological effects of THC and a lipophilic cannabis extract on normal and insulin resistant 3T3-L1 adipocytes.

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“Type 2 diabetes, a chronic disease, affects about 150 million people world wide.

It is characterized by insulin resistance of peripheral tissues such as liver, skeletal muscle, and fat. Insulin resistance is associated with elevated levels of tumor necrosis factor alpha (TNF-alpha), which in turn inhibits insulin receptor tyrosine kinase autophosphorylation.

It has been reported that cannabis is used in the treatment of diabetes.

A few reports indicate that smoking cannabis can lower blood glucose in diabetics.

Delta(9)-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis.”

http://www.ncbi.nlm.nih.gov/pubmed/19345076

Cannabinoids for Symptom Management and Cancer Therapy: The Evidence.

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“Cannabinoids bind not only to classical receptors (CB1 and CB2) but also to certain orphan receptors (GPR55 and GPR119), ion channels (transient receptor potential vanilloid), and peroxisome proliferator-activated receptors. Cannabinoids are known to modulate a multitude of monoamine receptors. Structurally, there are 3 groups of cannabinoids.

Multiple studies, most of which are of moderate to low quality, demonstrate that tetrahydrocannabinol (THC) and oromucosal cannabinoid combinations of THC and cannabidiol (CBD) modestly reduce cancer pain.

Dronabinol and nabilone are better antiemetics for chemotherapy-induced nausea and vomiting (CINV) than certain neuroleptics, but are not better than serotonin receptor antagonists in reducing delayed emesis, and cannabinoids have largely been superseded by neurokinin-1 receptor antagonists and olanzapine; both cannabinoids have been recommended for breakthrough nausea and vomiting among other antiemetics. Dronabinol is ineffective in ameliorating cancer anorexia but does improve associated cancer-related dysgeusia.

Multiple cancers express cannabinoid receptors directly related to the degree of anaplasia and grade of tumor.

Preclinical in vitro and in vivo studies suggest that cannabinoids may have anticancer activity.

Paradoxically, cannabinoid receptor antagonists also have antitumor activity.

There are few randomized smoked or vaporized cannabis trials in cancer on which to judge the benefits of these forms of cannabinoids on symptoms and the clinical course of cancer. Smoked cannabis has been found to contain Aspergillosis. Immunosuppressed patients should be advised of the risks of using “medical marijuana” in this regard.”

http://www.ncbi.nlm.nih.gov/pubmed/27407130

Cannabinoid receptor 1 binding activity and quantitative analysis of Cannabis sativa L. smoke and vapor.

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“Cannabis sativa L. (cannabis) extracts, vapor produced by the Volcano vaporizer and smoke made from burning cannabis joints were analyzed by GC-flame ionization detecter (FID), GC-MS and HPLC. Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol.

Cannabinoids plus other components such as terpenoids and pyrolytic by-products were identified and quantified in all samples. Cannabis vapor and smoke was tested for cannabinoid receptor 1 (CB1) binding activity and compared to pure Delta(9)-tetrahydrocannabinol (Delta(9)-THC).

The top five major compounds in Bedrocan extracts were Delta(9)-THC, cannabigerol (CBG), terpinolene, myrcene, and cis-ocimene in Bedrobinol Delta(9)-THC, myrcene, CBG, cannabichromene (CBC), and camphene in Bediol cannabidiol (CBD), Delta(9)-THC, myrcene, CBC, and CBG.

The major components in Bedrocan vapor (>1.0 mg/g) were Delta(9)-THC, terpinolene, myrcene, CBG, cis-ocimene and CBD in Bedrobinol Delta(9)-THC, myrcene and CBD in Bediol CBD, Delta(9)-THC, myrcene, CBC and terpinolene.

The major components in Bedrocan smoke (>1.0 mg/g) were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene.

There was no statistically significant difference between CB1 binding of pure Delta(9)-THC compared to cannabis smoke and vapor at an equivalent concentration of Delta(9)-THC.”

http://www.ncbi.nlm.nih.gov/pubmed/20118579

The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation.

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“The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (-)-Δ(9)-tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure-CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure-activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure-activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles.”

http://www.ncbi.nlm.nih.gov/pubmed/27398024

Inhibition of the cataleptic effect of tetrahydrocannabinol by other constituents of Cannabis sativa L.

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“Tetrahydrocannabinol (THC) induced catalepsy in mice, whereas a cannabis oil (6.68% w/w THC), four cannabinoids and a synthetic mixture did not. Cannabinol (CBN) and olivetol inhibited THC-induced catalepsy in the mornings and the evenings, but cannabidiol (CBD) exhibited this effect only in the evenings. A combination of CBN and CBD inhibited THC-induced catalepsy equal to that of CBN alone in the mornings, but this inhibition was greater than that produced by CBN alone in the evenings.”  http://www.ncbi.nlm.nih.gov/pubmed/2897447