Category Archives: Addiction

Brain cannabinoid receptor 2: expression, function and modulation.

Posted on by
Reply

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

Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists.

Posted on by
Reply

Image result for neuropharmacology journal

“The misuse of prescription opiates is on the rise with combination therapies (e.g. acetaminophen or NSAIDs) resulting in severe liver and kidney damage. In recent years, cannabinoid receptors have been identified as potential modulators of pain and rewarding behaviors associated with cocaine, nicotine and ethanol in preclinical models. Yet, few studies have identified whether mu opioid agonists and CB2 agonists act synergistically to inhibit chronic pain while reducing unwanted side effects including reward liability.

We determined if analgesic synergy exists between the mu-opioid agonist morphine and the selective CB2 agonist, JWH015, in rodent models of acute and chronic inflammatory, post-operative, and neuropathic pain using isobolographic analysis. We also investigated if the MOR-CB2 agonist combination decreased morphine-induced conditioned place preference (CPP) and slowing of gastrointestinal transit. Co-administration of morphine with JWH015 synergistically inhibited preclinical inflammatory, post-operative and neuropathic-pain in a dose- and time-dependent manner; no synergy was observed for nociceptive pain. Opioid-induced side effects of impaired gastrointestinal transit and CPP were significantly reduced in the presence of JWH015.

Here we show that MOR + CB2 agonism results in a significant synergistic inhibition of preclinical pain while significantly reducing opioid-induced unwanted side effects.

The opioid sparing effect of CB2 receptor agonism strongly supports the advancement of a MOR-CB2 agonist combinatorial pain therapy for clinical trials.”

https://www.ncbi.nlm.nih.gov/pubmed/28007501

Smoking cannabis ‘helps addicts give up heroin’, study finds

Posted on by
Reply

Smoking cannabis ‘helps addicts give up heroin’, study finds

“Smoking weed helps patients give up opiates such as heroin, a new study has found.

Researchers at Columbia University monitored patients undergoing treatment for opiate addiction – and found that patients who smoked weed were more able to sleep, less anxious, and more likely to complete their course.

 The researchers also found that dosing patients with dronabinol – a drug consisting of the ‘active’ ingredient in cannabis, THC – helped with withdrawal symptoms.”

http://metro.co.uk/2015/12/02/smoking-cannabis-helps-addicts-give-up-heroin-study-finds-5538896/

A novel inhibitor of endocannabinoid catabolic enzymes sheds light on behind the scene interplay between chronic pain, analgesic tolerance, and heroin dependence.

Posted on by
Reply

Image result for Neuropharmacology.

“From the Aristotelian ancient Greece, pain has been associated with appetites or emotions and is opposite to pleasure. Reward and addiction is also linked to pleasure and compulsive drug seeking reinstates pleasure.

Alleviation of chronic pain can induce a euphoric phase similar to what is found in addiction. Both chronic pain and addiction are recognized as a disease of the central nervous system. They share many characteristics and brain regions/mechanisms.

Evidence points to the usefulness of cannabinoids as a new class of agents to add to the pharmaceutical toolbox in the management of chronic pain.

Wilkerson and colleagues, in this issue, examine SA-57, an inhibitor of two different endocannabinoid catabolic enzymes FAAH and MAGL, demonstrating its analgesic effectiveness and morphine-sparing properties in a chronic pain model, as well as its ability to reduce heroin seeking behavior in a self-administration paradigm in mice.

This timely study emphasizes the need for development of more efficacious chronic pain therapeutics with minimized abuse potential and/or reinforcing properties. It also highlights the need for better understanding of the overlapping circuitry of chronic pain, reward, and addiction.”

https://www.ncbi.nlm.nih.gov/pubmed/27890603

The endocannabinoid hydrolysis inhibitor SA-57: Intrinsic antinociceptive effects, augmented morphine-induced antinociception, and attenuated heroin seeking behavior in mice.

Posted on by
Reply

Image result for Neuropharmacology.

“Although opioids are highly efficacious analgesics, their abuse potential and other untoward side effects diminish their therapeutic utility. The addition of non-opioid analgesics offers a promising strategy to reduce required antinociceptive opioid doses that concomitantly reduce opioid-related side effects.

Inhibitors of the primary endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) show opioid-sparing effects in preclinical models of pain. As simultaneous inhibition of these enzymes elicits enhanced antinociceptive effects compared with single enzyme inhibition, the present study tested whether the dual FAAH-MAGL inhibitor SA-57 [4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester] produces morphine-sparing antinociceptive effects, without major side effects associated with either drug class.

Although high doses of SA-57 alone were required to produce antinociception, low doses of this compound, which elevated AEA and did not affect 2-AG brain levels, augmented the antinociceptive effects of morphine, but lacked cannabimimetic side effects.

Because of the high abuse liability of opioids and implication of the endocannabinoid system in the reinforcing effects of opioids, the final experiment tested whether SA-57 would alter heroin seeking behavior. Strikingly, SA-57 reduced heroin-reinforced nose poke behavior and the progressive ratio break point for heroin.

In conclusion, the results of the present study suggest that inhibition of endocannabinoid degradative enzymes represents a promising therapeutic approach to decrease effective doses of opioids needed for clinical pain control, and may also possess therapeutic potential to reduce opioid abuse.”

https://www.ncbi.nlm.nih.gov/pubmed/27890602

Smoking cannabis ‘may help alcoholics to quit drinking’

Posted on by
Reply

“Scientists have claimed that smoking weed may actually help alcoholics kick their drinking habit for good.

Despite cannabis being regarded by anti-drugs campaigners as a ‘gateway drug’ to more addictive and harder substances, experts at the University of British Columbia (UBC) in Canada think the opposite is true.

UBC researcher Zach Walsh explained: “Research suggests that people may be using cannabis as an exit drug to reduce the use of substances that are potentially more harmful, such as opioid pain medication.

“In reviewing the limited evidence on medical cannabis, it appears that patients and others who have advocated for cannabis as a tool for harm reduction and mental health have some valid points.””

https://uk.news.yahoo.com/smoking-cannabis-may-help-alcoholics-to-quit-drinking-114645222.html?soc_src=social-sh&soc_trk=fb

“Smoking Cannabis May HELP Treat Alcohol/Drug Addiction And Mental Health Disorders” http://jewishbusinessnews.com/2016/11/16/smoking-cannabis-may-help-alcoholics-to-quit-drinking/

“Smoking Marijuana Could Help Alcoholics and Opioid Addicts Treat Their Addictions” http://thescienceexplorer.com/brain-and-body/smoking-marijuana-could-help-alcoholics-and-opioid-addicts-treat-their-addictions

Medical cannabis and mental health: A guided systematic review

Posted on by
Reply

Image result for sciencedirect

“This review considers the potential influences of the use of cannabis for therapeutic purposes (CTP) on areas of interest to mental health professionals, with foci on adult psychopathology and assessment. We identified 31 articles relating to the use of CTP and mental health, and 29 review articles on cannabis use and mental health that did not focus on use for therapeutic purposes. Results reflect the prominence of mental health conditions among the reasons for CTP use, and the relative dearth of high-quality evidence related to CTP in this context, thereby highlighting the need for further research into the harms and benefits of medical cannabis relative to other therapeutic options. Preliminary evidence suggests that CTP may have potential for the treatment of PTSD, and as a substitute for problematic use of other substances. Extrapolation from reviews of non-therapeutic cannabis use suggests that the use of CTP may be problematic among individuals with psychotic disorders. The clinical implications of CTP use among individuals with mood disorders are unclear. With regard to assessment, evidence suggests that CTP use does not increase risk of harm to self or others. Acute cannabis intoxication and recent CTP use may result in reversible deficits with the potential to influence cognitive assessment, particularly on tests of short-term memory.

Cannabis use does not appear to increase risk of harm to self or others.”

http://www.sciencedirect.com/science/article/pii/S0272735816300939

“Marijuana could help treat drug addiction, mental health, study suggests”  https://www.sciencedaily.com/releases/2016/11/161116102847.htm

“Marijuana may help combat substance abuse, mental health disorders”  http://www.medicalnewstoday.com/articles/314159.php

“Medical cannabis may help treat mental health problems and opioid addiction”  http://www.news-medical.net/news/20161116/Medical-cannabis-may-help-treat-mental-health-problems-and-opioid-addiction.aspx

Crystal Structure of the Human Cannabinoid Receptor CB1.

Posted on by
Reply

Image result for cell journal

“Cannabinoid receptor 1 (CB1) is the principal target of Δ9-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use.

CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders.

Here, we present the 2.8 Å crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study.

The structure of the CB1-AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding.

In combination with functional studies and molecular modeling, the structure provides insight into the binding mode of naturally occurring CB1 ligands, such as THC, and synthetic cannabinoids.

This enhances our understanding of the molecular basis for the physiological functions of CB1 and provides new opportunities for the design of next-generation CB1-targeting pharmaceuticals.”

https://www.ncbi.nlm.nih.gov/pubmed/27768894

Cannabis as Secondary Drug Is Not Associated With a Greater Risk of Death in Patients With Opiate, Cocaine, or Alcohol Dependence.

Posted on by
Reply

Image result for Journal of Addiction Medicine

“To assess the impact of cannabis use as secondary drug on mortality of patients with other major substance use disorders.

Positive urinary cannabis did not confer an increased risk of death in patients with severe opiate, cocaine or alcohol dependence.”

https://www.ncbi.nlm.nih.gov/pubmed/27753720

State Medical Marijuana Laws and the Prevalence of Opioids Detected Among Fatally Injured Drivers.

Posted on by
Reply

Image result for Am J Public Health.

“To assess the association between medical marijuana laws (MMLs) and the odds of a positive opioid test, an indicator for prior use.

State-specific estimates indicated a reduction in opioid positivity for most states after implementation of an operational MML,

CONCLUSIONS:

Operational MMLs are associated with reductions in opioid positivity among 21- to 40-year-old fatally injured drivers and may reduce opioid use and overdose.”

http://www.ncbi.nlm.nih.gov/pubmed/27631755