Tag Archives: Delta-9-Tetrahydrocannabinol

A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment.

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“Peripheral neuropathic pain (PNP) associated with allodynia poses a significant clinical challenge. The efficacy of Δ9 -tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray, a novel cannabinoid formulation, was investigated in this 15-week randomized, double-blind, placebo-controlled parallel group study…

These findings demonstrate that, in a meaningful proportion of otherwise treatment-resistant patients, clinically important improvements in pain, sleep quality and SGIC of the severity of their condition are obtained with THC/CBD spray. THC/CBD spray was well tolerated and no new safety concerns were identified.”

http://www.ncbi.nlm.nih.gov/pubmed/24420962

Modulation of Gut-Specific Mechanisms by Chronic Δ9-THC Administration in Male Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Systems Biology Analysis.

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“Our studies have demonstrated that chronic Δ9-tetrahydrocannabinol (THC) administration results in a generalized attenuation of viral load and tissue inflammation in simian immunodeficiency virus (SIV)-infected male rhesus macaques…

Our results indicate that chronic THC treatment modulated duodenal T cell populations, favored a pro-Th2 cytokine balance, and decreased intestinal apoptosis.

These findings reveal novel mechanisms that may potentially contribute to cannabinoid-mediated disease modulation.”

http://www.ncbi.nlm.nih.gov/pubmed/24400995

“Previous studies from our laboratory have shown that chronic THC administration ameliorates SIV disease progression and significantly reduces the morbidity and mortality of male SIV-infected macaques… In summary, using a systems biology approach to understanding the impact of chronic cannabinoid treatment on gut-associated immunopathology, we identified relevant mechanisms that can potentially modulate disease progression. Our results suggest that gut immunomodulation through changes in gene expression, cytokine profiles, and immune cell populations could potentially contribute to chronic THC modulation of SIV disease progression. Moreover, they reveal novel mechanisms that may potentially contribute to decreased morbidity and mortality.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046212/

Sativex(®) (tetrahydrocannabinol + cannabidiol), an endocannabinoid system modulator: basic features and main clinical data.

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“Sativex(®) (nabiximols, USAN name) oromucosal spray contains the two main active constituents of Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 molecular ratio, and acts as an endocannabinoid system modulator. Randomized, controlled clinical trials of Sativex as add-on therapy provide conclusive evidence of its efficacy in the treatment of more than 1500 patients with multiple sclerosis (MS)-related resistant spasticity…

Sativex oromucosal spray appears to be a useful and welcomed option for the management of resistant spasticity in MS patients. Although the management of MS has been improved by the availability of disease-modifying agents that target the underlying pathophysiological processes of the disease, a clear need remains for more effective symptomatic treatments, especially as regards MS-related spasticity and pain.”

http://www.ncbi.nlm.nih.gov/pubmed/21449855

Chronic administration during early adulthood does not alter the hormonally-dependent disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on complex behavior in female rats.

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“This study examined whether chronic Δ9-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ9-THC during adolescence…

no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ9-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we and others have shown for chronic administration during adolescence.”

http://www.ncbi.nlm.nih.gov/pubmed/24361784

The endocannabinoid system, cannabinoids, and pain.

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“The endocannabinoid system is involved in a host of homeostatic and physiologic functions, including modulation of pain and inflammation… Exogenous plant-based cannabinoids (phytocannabinoids) and chemically related compounds, like the terpenes, commonly found in many foods, have been found to exert significant analgesic effects in various chronic pain conditions.

Currently, the use of Δ9-tetrahydrocannabinol is limited by its psychoactive effects and predominant delivery route (smoking), as well as regulatory or legal constraints.

 However, other phytocannabinoids in combination, especially cannabidiol and β-caryophyllene, delivered by the oral route appear to be promising candidates for the treatment of chronic pain due to their high safety and low adverse effects profiles.

This review will provide the reader with the foundational basic and clinical science linking the endocannabinoid system and the phytocannabinoids with their potentially therapeutic role in the management of chronic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/24228165

Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas.

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“To evaluate, through a systematic review of the literature, the antitumoral effects of cannabinoids on gliomas…

  In all experimental studies included, cannabinoids exerted antitumoral activity in vitro and/or antitumoral evidence in vivo in several models of tumor cells and tumors.

The antitumor activity included: antiproliferative effects (cell cycle arrest), decreased viability and cell death by toxicity, apoptosis, necrosis, autophagy, as well as antiangiogenic and antimigratory effects.

 Antitumoral evidence included: reduction in tumor size, antiangiogenic, and antimetastatic effects.

 Additionally, most of the studies described that the canabinnoids exercised selective antitumoral action in several distinct tumor models. Thereby, normal cells used as controls were not affected.

The safety factor in the cannabinoids’ administration has also been demonstrated in vivo.

 The various cannabinoids tested in multiple tumor models showed antitumoral effects both in vitro and in vivo.

 These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.”

http://www.ncbi.nlm.nih.gov/pubmed/24142199

Δ9-TETRAHYDROCANNABINOL IS PROTECTIVE THROUGH PPARγ DEPENDENT MITOCHONDRIAL BIOGENESIS IN A CELL CULTURE MODEL OF PARKINSON’S DISEASE

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“Cannabinoids such as Δ9-tetrahydrocannabinol (Δ9-THC) are neuroprotective in animal and cell culture models of Parkinson’s disease (PD).

In a PD cell culture model we recently demonstrated that Δ9-THC is neuroprotective through activation of the nuclear receptor peroxisomal proliferator-activated receptor γ (PPARγ)…

Here we investigate the effect of Δ9-THC and pioglitazone on mitochondrial biogenesis…

CONCLUSIONS:

Even though Δ9-THC and pioglitazone are both protective against MPP+ only Δ9-THC induces PPARγ dependent mitochondrial biogenesis, a mechanism that may be beneficial for the treatment of PD.”

http://jnnp.bmj.com/content/84/11/e2.58

“Δ⁹-tetrahydrocannabinol (Δ⁹-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson’s disease.” http://www.ncbi.nlm.nih.gov/pubmed/22236282

Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans.

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“Pre-extinction administration of Δ9-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely involves via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction…

 This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD.

 Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24055595

Cannabinoid facilitation of fear extinction memory recall in humans.

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“Animal studies have shown that activation of the cannabinoid system during extinction learning enhances fear extinction and its retention. Specifically, CB1 receptor agonists, such as Δ9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear…

 We conducted a study using a randomized, double-blind, placebo-controlled, between-subjects design, coupling a standard Pavlovian fear extinction paradigm and simultaneous skin conductance response (SCR) recording with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo (PBO) 2 h prior to extinction learning in 29 healthy adult volunteers (THC = 14; PBO = 15) and tested extinction retention 24 h after extinction learning.

Compared to subjects that received PBO, subjects that received THC showed low SCR to a previously extinguished CS when extinction memory recall was tested 24 h after extinction learning, suggesting that THC prevented the recovery of fear.

These results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing. This article is part of a Special Issue entitled ‘Cognitive Enhancers’.”

http://www.ncbi.nlm.nih.gov/pubmed/22796109

Clinical experiences with cannabinoids in spasticity management in multiple sclerosis.

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“Spasticity is a common symptom among patients with multiple sclerosis (MS). This study aims to assess the effectiveness and safety of the combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in clinical practice for the treatment of spasticity in MS…

Retrospective observational study with patients treated with inhaled THC/CBD…

 THC/CBD was effective in 80% of patients…

CONCLUSIONS:

THC/CBD appears to be a good alternative to standard treatment as it improves refractory spasticity in MS and has an acceptable toxicity profile.”

http://www.ncbi.nlm.nih.gov/pubmed/24035293