“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.”
Tag Archives: Delta-9-Tetrahydrocannabinol
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.”
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.”
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.”
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…
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.”
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/
THC:CBD Spray and MS Spasticity Symptoms: Data from Latest Studies.
“New clinical experience with 9-delta-tetrahydocannabinol (THC) and cannabidiol (CBD) oromucosal spray (Sativex®)…
A randomized, placebo controlled long-term follow-up clinical trial with THC:CBD spray versus placebo demonstrated that it was not associated with cognitive decline, depression or significant mood changes…
THC:CBD oromucosal spray did not adversely influence standard driving ability in patients with moderate to severe MS spasticity…
Findings to date reinforce the efficacy and safety observed in Phase III clinical trials…
Importantly, no additional safety concerns were identified…
Thus, these new data support a positive benefit-risk relationship for THC:CBD oromucosal spray during longer-term use.”
Δ(9)-THC and N-arachidonoyl glycine regulate BV-2 microglial morphology and cytokine release plasticity: implications for signaling at GPR18.
“Microglial cells are extremely plastic and undergo a variety of CNS-prompted shape changes relative to their location and current role. Signaling molecules from neurons also regulate microglial cytokine production. Neurons are known to employ the endogenous cannabinoid system to communicate with other cells of the CNS.
N-arachidonoyl glycine (NAGly) and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) signaling via GPR18 has been introduced as an important new target in microglial-neuronal communication…
These data add to an emerging profile that emphasizes NAGly as a component of an endogenous system present in the CNS that tightly integrates microglial proliferation, recruitment, and adhesion with neuron-glia interactivity and tissue remodeling.”