Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

“In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse.

This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/25801289

http://www.thctotalhealthcare.com/category/schizophrenia/

Δ9-Tetrahydrocannabinol alone and combined with cannabidiol mitigate fear memory through reconsolidation disruption.

“Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major constituents of the Cannabis sativa plant, which is frequently consumed by subjects exposed to life-threatening situations to relief their symptomatology.

It is still unknown, however, whether THC could also affect the maintenance of an aversive memory formed at that time when taken separately and/or in conjunction with CBD. The present study sought to investigate this matter at a preclinical level.

We report that THC (0.3-10mg/kg, i.p.) was able to disrupt the reconsolidation of a contextual fear memory, resulting in reduced conditioned freezing expression for over 22 days. This effect was dependent on activation of cannabinoid type-1 receptors located in prelimbic subregion of the medial prefrontal cortex and on memory retrieval/reactivation.

Since CBD may counteract the negative psychotropic effects induced by THC and has been shown to be a reconsolidation blocker, we then investigated and demonstrated that associating sub-effective doses of these two compounds was equally effective in attenuating fear memory maintenance in an additive fashion and in a dose ratio of 10 to 1, which contrasts with that commonly found in C. sativa recreational samples.

Of note, neither THC alone nor CBD plus THC interfered with anxiety-related behaviors and locomotor activity, as assessed in the elevated plus-maze test, at a time point coinciding with that used to evaluate their effects on memory reconsolidation.

Altogether, present findings suggest a potential therapeutic value of using THC and/or CBD to mitigate a dysfunctional aversive memory through reconsolidation disruption in post-traumatic stress disorder patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25799920

http://www.thctotalhealthcare.com/category/post-traumatic-stress-disorder-ptsd/

Endocannabinoid signaling at the periphery: 50 years after THC.

“In 1964, the psychoactive ingredient of Cannabis sativa, Δ9-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide) (AEA) in 1992 and 2-arachidonoylglycerol (2-AG) in 1995.

Since then, considerable research has shed light on the impact of eCBs on human health and disease, identifying an ensemble of proteins that bind, synthesize, and degrade them and that together form the eCB system (ECS). eCBs control basic biological processes including cell choice between survival and death and progenitor/stem cell proliferation and differentiation.

Unsurprisingly, in the past two decades eCBs have been recognized as key mediators of several aspects of human pathophysiology and thus have emerged to be among the most widespread and versatile signaling molecules ever discovered.

Here some of the pioneers of this research field review the state of the art of critical eCB functions in peripheral organs. Our community effort is aimed at establishing consensus views on the relevance of the peripheral ECS for human health and disease pathogenesis, as well as highlighting emerging challenges and therapeutic hopes.”

http://www.ncbi.nlm.nih.gov/pubmed/25796370

The endocannabinoid system and its therapeutic implications in rheumatoid arthritis.

“Since the discovery of the endogenous receptor for Δ9-tetrahydrocannabinol, a main constituent of marijuana, the endocannabinoid system (comprising cannabinoid receptors and their endogenous ligands, as well as the enzymes involved in their metabolic processes) has been implicated as having multiple regulatory functions in many central and peripheral conditions, including rheumatoid arthritis (RA).

RA is an immune-mediated inflammatory disease that is associated with the involvement of many kinds of cells (such as fibroblastlike synoviocytes [FLSs], osteoclasts, T cells, B cells, and macrophages) and molecules (such as interleukin-1β, tumor necrosis factor-α, interleukin-6, matrix metalloproteinases [MMPs], and chemokines). Increasing evidence suggests that the endocannabinoid system, especially cannabinoid receptor 2 (CB2), has an important role in the pathophysiology of RA.

Many members of the endocannabinoid system are reported to inhibit synovial inflammation, hyperplasia, and cartilage destruction in RA.

In particular, specific activation of CB2 may relieve RA by inhibiting not only the production of autoantibodies, proinflammatory cytokines, and MMPs, but also bone erosion, immune response mediated by T cells, and the proliferation of FLSs.

In this review, we will discuss the possible functions of the endocannabinoid system in the modulation of RA, which may be a potential target for treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25791728

http://www.thctotalhealthcare.com/category/rheumatoid-arthritis-2/

 

Cannabinoid Replacement Therapy (CRT): Nabiximols (Sativex) as a novel treatment for cannabis withdrawal.

“Cannabis is a common recreational drug that is generally considered to have low addictive potential.

However an increasing number of cannabis users are seeking treatment for dependence on the drug.

There is interest in using agonist (substitution) pharmacotherapies to treat cannabis dependence and here we outline a novel approach involving a buccal spray (Nabiximols) that contains tetrahydrocannabinol (THC) and cannabidiol (CBD).

We review recent research with Nabiximols and highlight findings relevant to clinical practice.”

http://www.ncbi.nlm.nih.gov/pubmed/25777582

Cannabis in cancer care.

“Cannabis has been used in medicine for thousands of years prior to achieving its current illicit substance status.

Cannabinoids, the active components of Cannabis sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids), activating specific cannabinoid receptors, particularly CB1 found predominantly in the central nervous system and CB2 found predominantly in cells involved with immune function.

Delta-9-tetrahydrocannabinol, the main bioactive cannabinoid in the plant, has been available as a prescription medication approved for treatment of cancer chemotherapy-induced nausea and vomiting and anorexia associated with the AIDS wasting syndrome.

Cannabinoids may be of benefit in the treatment of cancer-related pain, possibly synergistic with opioid analgesics.

Cannabinoids have been shown to be of benefit in the treatment of HIV-related peripheral neuropathy, suggesting that they may be worthy of study in patients with other neuropathic symptoms.

Cannabinoids have a favorable drug safety profile, but their medical use is predominantly limited by their psychoactive effects and their limited bioavailability.”

http://www.ncbi.nlm.nih.gov/pubmed/25777363

http://www.thctotalhealthcare.com/category/cancer/

Cost-effectiveness of Sativex in multiple sclerosis spasticity: new data and application to Italy.

“This study aims to evaluate the cost-effectiveness of Sativex® (9-delta-tetrahydrocannabinol plus cannabidiol oromucosal spray) when used as add-on therapy for management of resistant MS-related spasticity in the context of the Italian healthcare system…

Sativex can be regarded as a cost-effective treatment option for patients with MS-related spasticity in Italy.”

http://www.ncbi.nlm.nih.gov/pubmed/25771713

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia

“In this randomized, double-blind, placebo-controlled, crossover trial, we evaluated the safety, pharmacodynamics, and pharmacokinetics of THC…

Older people with dementia and physical comorbidity could greatly benefit from the therapeutic application of cannabinoids. Recent studies have demonstrated that low doses of THC are effective in protecting the brain from neuroinflammation-induced cognitive damage.

Our findings suggest that low THC doses are safe and well tolerated by frail older persons with dementia.”

http://link.springer.com/article/10.1007/s00213-015-3889-y

“Our findings suggest that low THC doses are safe and well tolerated by frail older persons with dementia.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480847/

 

delta 9-tetrahydrocannabinol in clinical oncology.

“After anecdotal reports of marijuana’s providing antiemetic activity in cancer chemotherapy patients refractory to standard agents, orally administereddelta 9-tetrahydrocannabinol (THC) was formally studied by a number of investigators.

In six of seven well-controlled studies, orally administered THC was a superior antiemetic agent compared with control agents.

Overall, the benefits of orally administered THC use represent a major advance in antiemetic therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/6262541

http://www.thctotalhealthcare.com/category/cancer/

Antiemetic effect of delta 9-tetrahydrocannabinol in chemotherapy-associated nausea and emesis as compared to placebo and compazine.

“delta 9-Tetrahydrocannabinol (THC), prochlorperazine, and placebo were compared.

Nausea was absent in 40 of 55 patients receiving THC, in 8 of 55 patients receiving prochlorperazine, and in 5 of 55 in the placebo group.

THC appeared to be more efficacious in controlling the emesis associated with cyclophosphamide, 5-fluorouracil, and doxorubicin and less so for nitrogen mustard and the nitrosourea.

THC appears to offer significant control of nausea in most patients and exceeds by far that provided by prochlorperazine.”

http://www.ncbi.nlm.nih.gov/pubmed/6271846