Inhibition of adenylate cyclase by delta 9-tetrahydrocannabinol in mouse spleen cells: a potential mechanism for cannabinoid-mediated immunosuppression.

“The ability of delta 9-Tetrahydrocannabinol (delta 9-THC) to modulate adenylate cyclase activity in mouse spleen cells was investigated…

delta 9-THC treated spleen cells demonstrated a 33% inhibition and a 66% inhibition in intracellular cAMP… respectively…

These studies suggest that inhibition of immune function by delta 9-THC may be mediated through the inhibition of intracellular cAMP early after antigen stimulation.”

http://www.ncbi.nlm.nih.gov/pubmed/1321935

Cannabinoid inhibition of adenylate cyclase. Biochemistry of the response in neuroblastoma cell membranes.

“The inhibition of adenylate cyclase activity by cannabimimetic compounds in a membrane fraction from cultured neuroblastoma cells has been examined. The inhibition was shown to be concentration-dependent over a nanomolar range for both delta 9-tetrahydrocannabinol and its synthetic analog…

This study points to the similarities between the enzyme inhibition by cannabimimetic compounds and by muscarinic cholinergic compounds. It is inferred that the cannabimimetic compounds must act via regulatory mechanisms similar to those operating for receptor-mediated inhibition of adenylate cyclase.”

http://www.ncbi.nlm.nih.gov/pubmed/2984538

Cannabinoid inhibition of adenylate cyclase: relative activity of constituents and metabolites of marihuana.

“delta 9Tetrahydrocannabinol (THC) has been shown to inhibit the activity of adenylate cyclase in the N18TG2 clone of murine neuroblastoma cells. The concentration of delta 9THC exhibiting half-maximal inhibition was 500 nM. delta 8Tetrahydrocannabinol was less active, and cannabinol was only partially active. Cannabidiol, cannabigerol, cannabichromene, olivetol and compounds having a reduced length of the C3 alkyl side chain were inactive. The metabolites of delta 8THC and delta 9THC hydroxylated at the C11 position were more potent than the parent drugs. However, hydroxylation at the C8 position of the terpenoid ring resulted in loss of activity. Compounds hydroxylated along the C3 alkyl side chain were equally efficacious but less potent than delta 9THC. These findings are compared to the pharmacology of cannabinoids reported for psychological effects in humans and behavioral effects in a variety of animal models.”

http://www.ncbi.nlm.nih.gov/pubmed/3601007

Thermal isomerization of cannabinoid analogues.

“Thermal isomerization of CBC(an) to THC(an) [nonaromatic analogues of plant cannabinoids cannabichromene (CBC) and Delta(1)-tetrahydrocannabinol (THC), respectively] is predicted in silico and demonstrated experimentally. Density functional theory calculations support a similar isomerization mechanism for the corresponding plant cannabinoids. Docking studies suggest that THC(an), although nonaromatic, has a CB(1) receptor binding affinity similar to that of natural THC.”

http://www.ncbi.nlm.nih.gov/pubmed/19919138

Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation.

“Plant cannabinoids, like Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), activate/desensitize thermosensitive transient receptor potential (TRP) channels of vanilloid type-1 or -2 (TRPV1 or TRPV2). We investigated whether cannabinoids also activate/desensitize two other ‘thermo-TRP’s’, the TRP channels of vanilloid type-3 or -4 (TRPV3 or TRPV4), and if the TRPV-inactive cannabichromene (CBC) modifies the expression of TRPV1-4 channels in the gastrointestinal tract…

CONCLUSIONS:

Cannabinoids can affect both the activity and the expression of TRPV1-4 channels, with various potential therapeutic applications, including in the gastrointestinal tract.”

http://www.ncbi.nlm.nih.gov/pubmed/21726418

Peripheral, but not central effects of cannabidiol derivatives: mediation by CB(1) and unidentified receptors.

“Delta-9 tetrahydrocannabinol (Delta(9)-THC) and (-)-cannabidiol ((-)-CBD) are major constituents of the Cannabis sativa plant with different pharmacological profiles…

We tested a series of (+)- and (-)-CBD derivatives for central and peripheral effects in mice…

We suggest that (+)-CBD analogues have mixed agonist/antagonist activity in the brain.

Second, (-)-CBD analogues which are devoid of cannabinoid receptor affinity but which inhibit intestinal motility, suggest the existence of a non-CB(1), non-CB(2) receptor.

Therefore, such analogues should be further developed as antidiarrheal and/or antiinflammatory drugs.

We propose to study the therapeutic potential of (-)- and (+)-CBD derivatives for complex conditions such as inflammatory bowel disease and cystic fibrosis.”

http://www.ncbi.nlm.nih.gov/pubmed/15910887

Δ9-Tetrahydrocannabinol Treatment During Human Monocyte Differentiation Reduces Macrophage Susceptibility to HIV-1 Infection

“The major psychoactive component of marijuana, Δ9-tetrahydrocannabinol (THC), also acts to suppress inflammatory responses. Receptors for THC, CB1, CB2, and GPR55, are differentially expressed on multiple cell types including monocytes and macrophages, which are important modulators of inflammation in vivo and target cells for HIV-1 infection. Use of recreational and medicinal marijuana is increasing, but the consequences of marijuana exposure on HIV-1 infection are unclear. Ex vivo studies were designed to investigate effects on HIV-1 infection in macrophages exposed to THC during or following differentiation.

THC treatment of primary human monocytes during differentiation reduced HIV-1 infection…

THC treatment of monocytes during differentiation into MDMs suppresses HIV-1 infection. 
Ultimately, the mechanism of THC suppression of HIV-1 infection was traced to a reduction in cell surface HIV receptor (CD4, CCR5 and CXCR4) expression that diminished entry efficiency.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019698/

Cannabinoids inhibit cholinergic contraction in human airways through prejunctional CB1 receptors

“Here, we sought to assess the effects of natural and synthetic cannabinoids on cholinergic bronchial contraction…

Delta-9-tetrahydrocannabinol, WIN55,212-2 and CP55,940 induced concentration-dependent inhibition of cholinergic contraction… 

Conclusions and implications

Activation of prejunctional CB1-receptors appears to mediate the inhibition of electrical field stimulation-evoked cholinergic contraction in human bronchus.

This feature may explain the acute bronchodilation produced by marijuana smoking.”

http://onlinelibrary.wiley.com/doi/10.1111/bph.12597/abstract

Use of Dronabinol for Cannabis Dependence: Two Case Reports and Review

“Based on recent laboratory studies, dronabinol (delta-9-tetrahydrocannabinol) has been shown to reduce cannabis withdrawal symptoms and the subjective effects of marijuana.

Given that agonist agents have been found to be effective for opiate and nicotine dependence, the clinical utility of dronabinol for cannabis dependence is a reasonable approach…

It is clear from the two cases that both patients found the induction onto dronabinol helpful.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733248/

Dronabinol for the Treatment of Cannabis Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

“… there are no effective medications for cannabis dependence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, in treating cannabis dependence.

This is the first trial using an agonist substitution strategy for treatment of cannabis dependence. Dronabinol showed promise, it was well-tolerated, and improved treatment retention and withdrawal symptoms…

In conclusion, agonist substitution pharmacotherapy with dronabinol, a synthetic form of THC, showed promise for treatment of cannabis dependence, reducing withdrawal symptoms and improving retention in treatment…

The trial showed that among adult cannabis-dependent patients, dronabinol was well accepted, with good adherence and few adverse events.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154755/