Category Archives: Addiction

Endocannabinoid System and Alcohol Abuse Disorders.

Posted on by
Reply

“Δ9-tetrahydrocannabinol (Δ9-THC), the primary active component in Cannabis sativa preparations such as hashish and marijuana, signals by binding to cell surface receptors. Two types of receptors have been cloned and characterized as cannabinoid (CB) receptors. CB1 receptors (CB1R) are ubiquitously present in the central nervous system (CNS) and are present in both inhibitory interneurons and excitatory neurons at the presynaptic terminal. CB2 receptors (CB2R) are demonstrated in microglial cells, astrocytes, and several neuron subpopulations and are present in both pre- and postsynaptic terminals.

The majority of studies on these receptors have been conducted in the past two and half decades after the identification of the molecular constituents of the endocannabinoid (eCB) system that started with the characterization of CB1R. Subsequently, the seminal discovery was made, which suggested that alcohol (ethanol) alters the eCB system, thus establishing the contribution of the eCB system in the motivation to consume ethanol. Several preclinical studies have provided evidence that CB1R significantly contributes to the motivational and reinforcing properties of ethanol and that the chronic consumption of ethanol alters eCB transmitters and CB1R expression in the brain nuclei associated with addiction pathways.

Additionally, recent seminal studies have further established the role of the eCB system in the development of ethanol-induced developmental disorders, such as fetal alcohol spectrum disorders (FASD). These results are augmented by in vitro and ex vivo studies, showing that acute and chronic treatment with ethanol produces physiologically relevant alterations in the function of the eCB system during development and in the adult stage. This chapter provides a current and comprehensive review of the literature concerning the role of the eCB system in alcohol abuse disorders (AUD).”

https://www.ncbi.nlm.nih.gov/pubmed/31332736

https://link.springer.com/chapter/10.1007%2F978-3-030-21737-2_6

“Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742761/

Cannabis Use Motivations among Adults Prescribed Opioids for Pain versus Opioid Addiction.

Posted on by
Reply

Pain Management Nursing“Cannabis has been linked to reduced opioid use, although reasons for cannabis use among adults prescribed opioids are unclear.

The purpose of this study was to determine whether motivations for cannabis use differ between adults prescribed opioids for persistent pain versus those receiving opioids as medication-assisted treatment for opioid use disorder.

RESULTS:

More than half the sample (n = 122) reported current, daily cannabis use and 63% reported pain as a motivation for use. Adults with persistent pain were more likely to be older, female, and have higher levels of education (p < .05). Adults with opioid use disorder were more likely to report “enhancement” (p < .01) and relief of drug withdrawal symptoms (p < .001) as motivations for cannabis use. The most common reasons for cannabis use in both populations were social and recreational use and pain relief.

CONCLUSIONS:

Both studied populations have unmet health needs motivating them to use cannabis and commonly use cannabis for pain. Persistent pain participants were less likely to use cannabis for euphoric effects or withdrawal purposes. Nurses should assess for cannabis use, provide education on known risks and benefits, and offer options for holistic symptom management.”

https://www.ncbi.nlm.nih.gov/pubmed/31375419

https://www.painmanagementnursing.org/article/S1524-9042(19)30096-7/fulltext

Endocannabinoid Signaling in the Central Amygdala and Bed Nucleus of the Stria Terminalis: Implications for the Pathophysiology and Treatment of Alcohol Use Disorder.

Posted on by
Reply

Alcoholism: Clinical and Experimental Research banner“High rates of relapse are a chronic and debilitating obstacle to effective treatment of alcohol use disorder (AUD); however, no effective treatments are available to treat symptoms induced by protracted abstinence.

In the first part of this two-part review series, we examine the literature supporting the effects of alcohol exposure within the extended amygdala (EA) neural circuitry.

In part two, we focus in on a potential way to combat negative affect associated with AUD, by exploring the therapeutic potential of the endogenous cannabinoid (eCB) system.

The eCB system is a potent modulator of neural activity in the brain, and its ability to mitigate stress and negative affect has long been an area of interest for developing novel therapeutics.

This review details the recent advances in our understanding of eCB signaling in two key regions of the EA, the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST), and their role in regulating negative affect.

Despite an established role for EA eCB signaling in reducing negative affect, few studies have examined the potential for eCB-based therapies to treat AUD-associated negative affect.

In this review, we present an overview of studies focusing on eCB signaling in EA and cannabinoid modulation on EA synaptic activity. We further discuss studies suggesting dysregulation of eCB signaling in models of AUD and propose that pharmacological augmentation of eCB could be a novel approach to treat aspects of AUD.

Lastly, future directions are proposed to advance our understanding of the relationship between AUD-associated negative affect and the EA eCB system that could yield new pharmacotherapies targeting negative affective symptoms associated with AUD.”

https://www.ncbi.nlm.nih.gov/pubmed/31373708

https://onlinelibrary.wiley.com/doi/abs/10.1111/acer.14159

The Potential of Cannabidiol as a Treatment for Psychosis and Addiction: Who Benefits Most? A Systematic Review.

Posted on by
Reply

jcm-logo

“The endogenous cannabinoid (eCB) system plays an important role in the pathophysiology of both psychotic disorders and substance use disorders (SUDs). The non-psychoactive cannabinoid compound, cannabidiol (CBD) is a highly promising tool in the treatment of both disorders. Here we review human clinical studies that investigated the efficacy of CBD treatment for schizophrenia, substance use disorders, and their comorbidity. In particular, we examined possible profiles of patients who may benefit the most from CBD treatment. CBD, either as monotherapy or added to regular antipsychotic medication, improved symptoms in patients with schizophrenia, with particularly promising effects in the early stages of illness. A potential biomarker is the level of anandamide in blood. CBD and THC mixtures showed positive effects in reducing short-term withdrawal and craving in cannabis use disorders. Studies on schizophrenia and comorbid substance use are lacking. Future studies should focus on the effects of CBD on psychotic disorders in different stages of illness, together with the effects on comorbid substance use. These studies should use standardized measures to assess cannabis use. In addition, future efforts should be taken to study the relationship between the eCB system, GABA/glutamate, and the immune system to reveal the underlying neurobiology of the effects of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/31330972
https://www.mdpi.com/2077-0383/8/7/1058

Cannabidiol Treatment Might Promote Resilience to Cocaine and Methamphetamine Use Disorders: A Review of Possible Mechanisms.

Posted on by
Reply

molecules-logo“Currently, there are no approved pharmacotherapies for addiction to cocaine and other psychostimulant drugs. Several studies have proposed that cannabidiol (CBD) could be a promising treatment for substance use disorders.

In the present work, the authors describe the scarce preclinical and human research about the actions of CBD on the effects of stimulant drugs, mainly cocaine and methamphetamine (METH). Additionally, the possible mechanisms underlying the therapeutic potential of CBD on stimulant use disorders are reviewed.

CBD has reversed toxicity and seizures induced by cocaine, behavioural sensitization induced by amphetamines, motivation to self-administer cocaine and METH, context- and stress-induced reinstatement of cocaine and priming-induced reinstatement of METH seeking behaviours. CBD also potentiated the extinction of cocaine- and amphetamine-induced conditioned place preference (CPP), impaired the reconsolidation of cocaine CPP and prevented priming-induced reinstatement of METH CPP.

Observational studies suggest that CBD may reduce problems related with crack-cocaine addiction, such as withdrawal symptoms, craving, impulsivity and paranoia (Fischer et al., 2015). The potential mechanisms involved in the protective effects of CBD on addiction to psychostimulant drugs include the prevention of drug-induced neuroadaptations (neurotransmitter and intracellular signalling pathways changes), the erasure of aberrant drug-memories, the reversion of cognitive deficits induced by psychostimulant drugs and the alleviation of mental disorders comorbid with psychostimulant abuse. Further, preclinical studies and future clinical trials are necessary to fully evaluate the potential of CBD as an intervention for cocaine and methamphetamine addictive disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31315244

https://www.mdpi.com/1420-3049/24/14/2583

Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial.

Posted on by
Reply

Image result for jama network

“This study demonstrates that cannabinoid agonist treatment, in this case using nabiximols, in combination with psychosocial interventions is a safe approach for reducing cannabis use among individuals with cannabis dependence who are seeking treatment.”   https://www.ncbi.nlm.nih.gov/pubmed/31305874
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2737918
“nabiximols: An herbal preparation containing a defined quantity of specific cannabinoids formulated for oromucosal spray administration with potential analgesic activity. Nabiximols contains a standardized extract of tetrahydrocannabinol (THC), the non-psychoactive cannabinoid cannabidiol (CBD), other minor cannabinoids, flavonoids, and terpenes from two cannabis plant varieties.” https://www.cancer.gov/publications/dictionaries/cancer-drug/def/nabiximols
“Cannabis treatment counters addiction: First study of its kind. Trial shows cannabis replacement therapy can be effective” https://www.sciencedaily.com/releases/2019/07/190715114247.htm

Overcoming the psychiatric side effects of the cannabinoid CB1 receptor antagonists: Current approaches for therapeutics development.

Posted on by
Reply

“The cannabinoid receptor 1 (CBR1) is involved in a variety of physiological pathways and has long been considered a golden target for therapeutic manipulation. A large body of evidence in both animal and human studies suggests that CB1R antagonism is highly effective for the treatment of obesity, metabolic disorders and drug addiction. However, the first-in-class CB1R antagonist/inverse agonist, rimonabant, though demonstrating effectiveness for obesity treatment and smoking cessation, displays serious psychiatric side effects, including anxiety, depression and even suicidal ideation, resulting in its eventual withdrawal from the European market. Several strategies are currently being pursued to circumvent the mechanisms leading to these side effects by developing neutral antagonists, peripherally restricted ligands, and allosteric modulators. In this review, we describe the progress in the development of therapeutics targeting the cannabinoid receptor 1 in the last two decades.”

https://www.ncbi.nlm.nih.gov/pubmed/31284863

http://www.eurekaselect.com/173316/article

Distinct Functions of Endogenous Cannabinoid System in Alcohol Abuse Disorders.

Posted on by
Reply

British Journal of Pharmacology banner

“Δ9-tetrahydrocannabinol (Δ9 -THC), the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signaling by binding to cell surface receptors. CB1 receptors (CB1 s) are present in both inhibitory and excitatory presynaptic terminals. CB2 receptors (CB2 s) found in neuronal subpopulations in addition to microglial cells and astrocytes and are present in both pre- and postsynaptic terminals.

Subsequent to endocannabinoid (eCB) system discoveries, studies have suggested that alcohol alters the eCB system and that the eCB system plays a major role in the motivation to abuse alcohol.

Preclinical studies have provided evidence that chronic alcohol consumption modulates eCBs and CB1 expression in brain addiction circuits. In addition, studies have further established the distinct function of the eCB system in the development of fetal alcohol spectrum disorders. This review provides a recent and comprehensive assessment of the literature related to the function of the eCB system in alcohol abuse disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31265740

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14780

“Cannabis and Alcohol: From Basic Science to Public Policy.”  https://www.ncbi.nlm.nih.gov/pubmed/31265135

Use of Cannabis to Relieve Pain and Promote Sleep by Customers at an Adult Use Dispensary

Posted on by
Reply

Publication Cover

“Cannabis has been used for pain relief and to promote sleep for thousands of years. Over the past several decades in the United States (U.S.), a therapeutic role for cannabis in mainstream medicine has increasingly emerged. Medical cannabis patients consistently report using cannabis as a substitute for prescription medications. Both pain relief and sleep promotion are common reasons for cannabis use, and the majority of respondents who reported using cannabis for these reasons also reported decreasing or stopping their use of prescription or over-the-counter analgesics and sleep aids. While adult-use laws are frequently called “recreational,” implying that cannabis obtained through the adult use system is only for pleasure or experience-seeking, our findings suggest that many customers use cannabis for symptom relief.”

https://www.ncbi.nlm.nih.gov/pubmed/31264536

https://www.tandfonline.com/doi/full/10.1080/02791072.2019.1626953

“Cannabis Is An Effective Treatment Option For Pain Relief And Insomnia, Study Finds” https://www.inquisitr.com/5509672/cannabis-pain-medications-sleep/

“Marijuana Could Be The Alternative Pain Reliever Replacing Opioids”  https://www.medicaldaily.com/marijuana-alternative-pain-reliever-replacing-opioids-437974

Alcohol-induced conditioned place preference is modulated by CB2 cannabinoid receptors and modifies levels of endocannabinoids in the mesocorticolimbic system.

Posted on by
Reply

Pharmacology Biochemistry and Behavior

“The endocannabinoid (eCB) system is a particularly important neuronal mechanism implicated in alcohol use disorders. Animal models are key to broadening our knowledge of the neurobiological mechanisms underlying alcohol dependence.

This study has two main aims: i) to assess how eCB levels in different brain areas are modified by alcohol-induced conditioning place preference (CPP), and ii) to study how cannabinoid type 2 receptor (CB2R) is involved in alcohol-rewarding properties, using pharmacological manipulation in C57BL/6 mice.

Our results suggest that the eCB system is dysregulated throughout the mesocorticolimbic system by repeated alcohol exposure during the CPP paradigm, and that levels of anandamide (AEA) and several other N-acylethanolamines are markedly decreased in the medial prefrontal cortex and ventral midbrain of alcohol-CPP mice.

We also observed that the administering an antagonist/inverse agonist of the CB2R (AM630) during the acquisition phase of CPP reduced the rewarding effects of alcohol. However, activating CB2R signalling using the agonist JWH133 seems to reduce both alcohol- and food-rewarding behaviours. Therefore, our findings indicate that the rewarding effects of alcohol are related to its disruptive effect on AEA and other N-acylethanolamine signalling pathways.

Thus, pharmacological manipulation of CB2R is an interesting candidate treatment for alcohol use disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31220547

https://www.sciencedirect.com/science/article/pii/S0091305719300656?via%3Dihub