Brain cannabinoid CB₂ receptors modulate cocaine’s actions in mice.

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“These findings, for the first time, suggest that brain CB2 receptors modulate cocaine’s rewarding and locomotor-stimulating effects, likely by a DA-dependent mechanism.

Whatever the mechanisms, the present findings, for the first time, suggest that activation of brain CB2 receptors inhibits cocaine’s rewarding and psychomotor-stimulating effects, which is congruent with a rapidly expanding corpus of published reports implicating brain CB2 receptors in modulating a variety of CNS functions such as locomotion, pain, emesis, neurogenesis, and neuroprotection.

This finding not only challenges current views that CB2 receptors are absent from the CNS and that CB2 receptor ligands lack CNS effects, but also suggests that brain CB2 receptors may be a novel target for the pharmacotherapy of drug abuse and addiction.” http://europepmc.org/articles/pmc3164946

“Marijuana Could be Used to Treat Cocaine Addiction, According to Federal Research” http://www.laweekly.com/news/marijuana-could-be-used-to-treat-cocaine-addiction-according-to-federal-research-2392363

Cannabidiol reduces ethanol consumption, motivation and relapse in mice.

“This study evaluated the effects of cannabidiol (CBD) on ethanol reinforcement, motivation and relapse in C57BL/6 J mice. Taken together, these results reveal that the administration of CBD reduced the reinforcing properties, motivation and relapse for ethanol. These findings strongly suggest that CBD may result useful for the treatment of alcohol use disorders.” https://www.ncbi.nlm.nih.gov/pubmed/28194850

“Cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms.” http://www.sciencedirect.com/science/article/pii/S0891584913015670
“CBD is a main constituent of cannabis sativa. CBD is very well tolerated in humans. CBD has a plethora of actions, including anticonvulsive, anxiolytic, anti-relapse and neuroprotective properties, which make it an ideal candidate for treating multiple pathologies associated with alcohol use disorders.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096899/
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Adolescent exposure to chronic delta-9-tetrahydrocannabinol blocks opiate dependence in maternally deprived rats.

“Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during adolescence on this opiate vulnerability has not been investigated. Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC) exposure during postnatal days 35-49 was made in maternal deprived (D) or non-deprived rats. These findings point to the self-medication use of cannabis in subgroups of individuals subjected to adverse postnatal environment.” https://www.ncbi.nlm.nih.gov/pubmed/19553915 “The surprising effect of cannabis on morphine dependence. Injections of THC, the active principle of cannabis, eliminate dependence on opiates (morphine, heroin) in rats deprived of their mothers at birth.” https://medicalxpress.com/news/2009-07-effect-cannabis-morphine.html

“THC HELPS LAB RATS KICK THE MORPHINE HABIT”  http://hightimes.com/medicinal/thc-helps-lab-rats-kick-the-morphine-habit/

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Differential Expression of Endocannabinoid System-Related Genes in the Dorsal Hippocampus following Expression and Reinstatement of Morphine Conditioned Place Preference in Mice.

“The endocannabinoid signaling plays a critical role in mediating rewarding effects to morphine. The relative stability for the expression and reinstatement of morphine conditioned place preference (CPP) suggests the involvement of differential neuroadaptations in learned associations between environmental cues and morphine. Changes in gene expression in hippocampus through the endogenous cannabinoid system (eCB) may accompany and mediate the development of such neuroadaptations to repeated morphine stimulation. To test this possibility, we systematically compared the expression of eCB-related genes in the dorsal hippocampus following the expression, extinction, and reinstatement of morphine CPP using quantitative RT-PCR analyses. These results suggest that differential regulation of the synthesis and/or degradation of the eCB system contribute to the expression and reinstatement of morphine CPP.” https://www.ncbi.nlm.nih.gov/pubmed/28192193]]>

Cannabidiol: Swinging the Marijuana Pendulum From 'Weed' to Medication to Treat the Opioid Epidemic.

“Epidemics require a paradigm shift in thinking about all possible solutions. The rapidly changing sociopolitical marijuana landscape provides a foundation for the therapeutic development of medicinal cannabidiol to address the current opioid abuse crisis.” https://www.ncbi.nlm.nih.gov/pubmed/28162799]]>

Cannabidiol: Swinging the Marijuana Pendulum From ‘Weed’ to Medication to Treat the Opioid Epidemic.

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“Epidemics require a paradigm shift in thinking about all possible solutions. The rapidly changing sociopolitical marijuana landscape provides a foundation for the therapeutic development of medicinal cannabidiol to address the current opioid abuse crisis.”

https://www.ncbi.nlm.nih.gov/pubmed/28162799

Oral delta-9-tetrahydrocannabinol suppresses cannabis withdrawal symptoms.

“This study assessed whether oral administration of delta-9-tetrahydrocannbinol (THC) effectively suppressed cannabis withdrawal in an outpatient environment. The primary aims were to establish the pharmacological specificity of the withdrawal syndrome and to obtain information relevant to determining the potential use of THC to assist in the treatment of cannabis dependence.

METHOD:

Eight adult, daily cannabis users who were not seeking treatment participated in a 40-day, within-subject ABACAD study. Participants administered daily doses of placebo, 30 mg (10 mg/tid), or 90 mg (30 mg/tid) oral THC during three, 5-day periods of abstinence from cannabis use separated by 7-9 periods of smoking cannabis as usual.

RESULTS:

Comparison of withdrawal symptoms across conditions indicated that (1) the lower dose of THC reduced withdrawal discomfort, and (2) the higher dose produced additional suppression in withdrawal symptoms such that symptom ratings did not differ from the smoking-as-usual conditions. Minimal adverse effects were associated with either active dose of THC.

CONCLUSIONS:

This demonstration of dose-responsivity replicates and extends prior findings of the pharmacological specificity of the cannabis withdrawal syndrome. The efficacy of these doses for suppressing cannabis withdrawal suggests oral THC might be used as an intervention to aid cannabis cessation attempts.”  https://www.ncbi.nlm.nih.gov/pubmed/16769180

“The endocannabinoid system as a target for the treatment of cannabis dependence” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647947/

“Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report. CBD can be effective for the treatment of cannabis withdrawal syndrome.” https://www.ncbi.nlm.nih.gov/pubmed/23095052 “Oral delta-9-tetrahydrocannabinol suppresses cannabis withdrawal symptoms.” https://www.ncbi.nlm.nih.gov/pubmed/16769180]]>

Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers.

“Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability.

Overall, CBD did not display any signals of abuse liability at the doses tested and these data may help inform U.S. regulatory decisions regarding CBD schedule on the CSA.” https://www.ncbi.nlm.nih.gov/pubmed/28088032]]>

Brain cannabinoid receptor 2: expression, function and modulation.

Image result for Acta Pharmacol Sin. “Cannabis sativa (marijuana) is a fibrous flowering plant that produces an abundant variety of molecules, some with psychoactive effects. At least 4% of the world’s adult population uses cannabis annually, making it one of the most frequently used illicit drugs in the world. The psychoactive effects of cannabis are mediated primarily through cannabinoid receptor (CBR) subtypes. The prevailing view is that CB1Rs are mainly expressed in the central neurons, whereas CB2Rs are predominantly expressed in peripheral immune cells. However, this traditional view has been challenged by emerging strong evidence that shows CB2Rs are moderately expressed and function in specific brain areas. New evidence has demonstrated that brain CB2Rs modulate animal drug-seeking behaviors, suggesting that these receptors may exist in brain regions that regulate drug addiction. Recently, we further confirmed that functional CB2Rs are expressed in mouse ventral tegmental area (VTA) dopamine (DA) neurons and that the activation of VTA CB2Rs reduces neuronal excitability and cocaine-seeking behavior. In addition, CB2R-mediated modulation of hippocampal CA3 neuronal excitability and network synchronization has been reported. Here, we briefly summarize recent lines of evidence showing how CB2Rs modulate function and pathophysiology in the CNS.” https://www.ncbi.nlm.nih.gov/pubmed/28065934
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