Category Archives: Addiction

Reduced prevalence of alcoholic gastritis in hospitalized individuals who consume cannabis.

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“Alcoholic gastritis, a superficial erosive disease of the stomach, is a common manifestation of risky alcohol use. In contrast, cannabis which is frequently co-used with alcohol suppresses gastric acidity and might counteract the deleterious effect of alcohol on the gastric mucosa.

RESULTS:

Our study revealed that among risky alcohol users, cannabis co-users have a lower prevalence of alcoholic gastritis compared to non-cannabis users (1,289[1,169-1,421] vs. 1,723[1,583-1,875] per 100,000 hospitalizations for risky alcohol use), resulting in a 25% decreased probability of alcoholic gastritis (aRR:0.75[0.66-0.85]; p-value:<0.0001). Furthermore, dependent cannabis usage resulted in a lower prevalence of alcoholic gastritis when compared to both non-dependent-cannabis users (0.72[0.52-0.99]), and to non-cannabis-users (0.56[0.41-0.76]).

CONCLUSIONS:

We reveal that risky alcohol drinking combined with cannabis use is associated with reduced prevalence of alcohol-associated gastritis in patients. Given increased cannabis legislation globally, understanding if and how the specific ingredients in cannabis plant extract can be used in the treatment of alcoholic gastritis is paramount. In this regard, further molecular mechanistic studies are needed to delineate the mechanisms of our novel findings not only for alcoholic gastritis but also gastritis from other causes.”

https://www.ncbi.nlm.nih.gov/pubmed/30536396

https://onlinelibrary.wiley.com/doi/abs/10.1111/acer.13930

Behavioral effects of psychostimulants in mutant mice with cell-type specific deletion of CB2 cannabinoid receptors in dopamine neurons.

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Behavioural Brain Research

“Activation of the endocannabinoid system modulate dopaminergic pathways that are involved in the effects of psychostimulants including amphetamine, cocaine, nicotine and other drugs of abuse. Genetic deletion or pharmacological activation of CB2 cannabinoid receptor is involved in the modulation of the effects of psychostimulants and their rewarding properties. Taken together, our data suggest that CB2Rs play a role in the modulation of dopamine-related effects of psychostimulants and could be exploited as therapeutic target in psychostimulant addiction and other psychiatric disorders associated with dopamine dysregulation.”

https://www.ncbi.nlm.nih.gov/pubmed/30508607

https://www.sciencedirect.com/science/article/pii/S0166432818311987?via%3Dihub

Inhibition of Monoacylglycerol Lipase Reduces the Reinstatement of Methamphetamine-Seeking and Anxiety-Like Behaviors in Methamphetamine Self-Administered Rats.

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“Methamphetamine is a highly addictive psychostimulant with reinforcing properties. Our laboratory previously found that Δ8-tetrahydrocannabinol, an exogenous cannabinoid, suppressed the reinstatement of methamphetamine-seeking behavior.

The purpose of this study was to determine whether the elevation of endocannabinoids modulates the reinstatement of methamphetamine-seeking behavior and emotional changes in methamphetamine self-administered rats.

RESULTS:

JZL184 (32 and 40 mg/kg, i.p.), an inhibitor of monoacylglycerol lipase, significantly attenuated both the cue- and stress-induced reinstatement of methamphetamine-seeking behavior. Furthermore, URB597 (3.2 and 10 mg/kg, i.p.), an inhibitor of fatty acid amide hydrolase, attenuated only cue-induced reinstatement. AM251, a cannabinoid CB1 receptor antagonist, antagonized the attenuation of cue-induced reinstatement by JZL184 but not URB597. Neither JZL184 nor URB597 reinstated methamphetamine-seeking behavior when administered alone. In the elevated plus-maze test, rats that were in withdrawal from methamphetamine self-administration spent less time in the open arms. JZL184 ameliorated the decrease in time spent in the open arms.

CONCLUSION:

We showed that JZL184 reduced both the cue- and stress-induced reinstatement of methamphetamine-seeking and anxiety-like behaviors in rats that had self-administered methamphetamine. It was suggested that a decrease in 2-arachidonoylglycerol in the brain could drive the reinstatement of methamphetamine-seeking and anxiety-like behaviors.”

https://www.ncbi.nlm.nih.gov/pubmed/30481332

https://academic.oup.com/ijnp/advance-article/doi/10.1093/ijnp/pyy086/5210886

Disentangling longitudinal relations between youth cannabis use, peer cannabis use, and conduct problems: developmental cascading links to cannabis use disorder.

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“To determine whether cannabis use during adolescence can increase risk not only for cannabis use disorder (CUD) but also for conduct problems, potentially mediated by exposure to peers who use cannabis.

Change in cannabis use did not predict changes in conduct problems or peer cannabis use over time, controlling for gender, race-ethnicity and socio-economic status.

Cannabis use in adolescence does not appear to lead to greater conduct problems or association with cannabis-using peers apart from pre-existing conduct problems.

Instead, adolescents who (1) increasingly affiliate with cannabis-using peers or (2) have increasing levels of conduct problems are more likely to use cannabis, and this cascading chain of events appears to predict cannabis use disorder in emerging adulthood.”

https://www.ncbi.nlm.nih.gov/pubmed/30457181

https://onlinelibrary.wiley.com/doi/full/10.1111/add.14456

Patients’ and clinicians’ perspectives of co-use of cannabis and opioids for chronic non-cancer pain management in primary care.

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International Journal of Drug Policy

“The prevalence of opioid-associated morbidity and mortality underscores the need for research on non-opioid treatments for chronic non-cancer pain (CNCP). Pain is the most common medical condition for which patients request medical cannabis. Limited research indicates that patients are interested in cannabis as a potential addition to or replacement for opioid medication. This analysis reports on CNCP patient and clinician perceptions about the co-use of cannabis and opioids for CNCP management.

METHODS:

We interviewed 23 clinicians and 46 CNCP patients, using semi-structured interview guides, from six safety-net clinics across the San Francisco Bay Area, and 5 key stakeholders involved in CNCP management. We used a modified grounded theory approach to code and analyze transcripts.

RESULTS:

CNCP patients described potential benefits of co-use of cannabis and opioids for pain management and concerns about dosing and addictive potential. Patients reported seeking cannabis when unable to obtain prescription opioids. Clinicians stated that their patients reported cannabis being helpful in managing pain symptoms. Clinicians expressed concerns about the potential exacerbation of mental health issues resulting from cannabis use.

CONCLUSION:

Clinicians are hampered by a lack of clinically relevant information about cannabis use, efficacy and side-effects. Currently no guidelines exist for clinicians to address opioid and cannabis co-use, or to discuss the risk and benefits of cannabis for CNCP management, including side effects. Cannabis and opioid co-use was commonly reported by patients in our sample, yet rarely addressed during clinical CNCP care. Further research is needed on the risks and benefits of cannabis and opioid co-use.”

https://www.ncbi.nlm.nih.gov/pubmed/30472467

https://www.sciencedirect.com/science/article/pii/S0955395918302287

IMPACT OF NEUROIMMUNE ACTIVATION INDUCED BY ALCOHOL OR DRUG ABUSE ON ADOLESCENT BRAIN DEVELOPMENT.

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International Journal of Developmental Neuroscience

“Evidence obtained in recent decades has demonstrated that the brain still matures in adolescence. Changes in neural connectivity occur in different regions, including cortical and subcortical structures, which undergo modifications in white and gray matter densities. These alterations concomitantly occur in some neurotransmitter systems and hormone secretion, which markedly influence the refinement of certain brain areas and neural circuits.

The immaturity of the adolescent brain makes it more vulnerable to the effects of alcohol and drug abuse, whose use can trigger long-term behavioral dysfunction.

This article reviews the action of alcohol and drug abuse (cannabis, cocaine, opioids, amphetamines, anabolic androgenic steroids) in the adolescent brain, and their impact on both cognition and behavioral dysfunction, including predisposition to drug abuse in later life. It also discusses recent evidence that indicates the role of the neuroimmune system response and neuroinflammation as mechanisms that participate in many actions of ethanol and drug abuse in adolescence, including the neurotoxicity and alterations in neurocircuitry that contribute to the dysfunctional behaviors associated with addiction.

The new data suggest the therapeutic potential of anti-inflammatory targets to prevent the long-term consequences of drug abuse in adolescence.”

https://www.ncbi.nlm.nih.gov/pubmed/30468786

https://www.sciencedirect.com/science/article/pii/S073657481830251X?via%3Dihub

“Cannabinoids as novel anti-inflammatory drugs.”  https://www.ncbi.nlm.nih.gov/pubmed/20191092

Anti-inflammatory agents for smoking cessation? Focus on cognitive deficits associated with nicotine withdrawal in male mice.

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 Brain, Behavior, and Immunity

“Nicotine withdrawal is associated with cognitive deficits including attention, working memory, and episodic memory impairments.

Treatment with the non-psychoactive cannabinoid cannabidiol abolished memory impairment of nicotine withdrawal and microglia reactivity, reduced the expression of IL1β and IFNγ in the hippocampus and the prefrontal cortex, respectively, and normalized Ki67 levels. The nonsteroidal anti-inflammatory drug indomethacin also prevented cognitive deficits and microglial reactivity during withdrawal.

These data underline the usefulness of anti-inflammatory agents to improve cognitive performance during early nicotine abstinence.”

https://www.ncbi.nlm.nih.gov/pubmed/30391635

https://www.sciencedirect.com/science/article/pii/S0889159118302599?via%3Dihub

Adolescent THC exposure does not sensitize conditioned place preferences to subthreshold d-amphetamine in male and female rats.

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 Click to expand“The acute effects of marijuana consumption on brain physiology and behaviour are well documented, but the long-term effects of its chronic use are less well known. Chronic marijuana use during adolescence is of increased interest, given that the majority of individuals first use marijuana during this developmental stage , and  adolescent marijuana use is thought to increase the susceptibility to abusing other drugs when exposed later in life. It is possible that marijuana use during critical periods in adolescence could lead to increased sensitivity to other drugs of abuse later on. To test this, we chronically administered ∆ 9-tetrahydrocannabinol (THC) to male and female Long-Evans (LER) and Wistar (WR) rats directly after puberty onset. Rats matured to postnatal day 90 before being exposed to a conditioned place preference task (CPP). A subthreshold dose of d-amphetamine, found not to induce place preference in drug naïve rats, was used as the unconditioned stimulus. The effect of d-amphetamine on neural activity was inferred by quantifying cfos expression in the nucleus accumbens and dorsal hippocampus following CPP training. Chronic exposure to THC post-puberty had no potentiating effect on a subthreshold dose of d-amphetamine to induce CPP. No differences in cfosexpression were observed. These results show that chronic exposure to THC during puberty did not increase sensitivity to a sub-threshold dose of d-amphetamine in adult LER and WR rats. This supports the concept that THC may not sensitize the response to all drugs of abuse.”

https://www.ncbi.nlm.nih.gov/pubmed/29770212.2

https://f1000research.com/articles/7-342/v2

Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age.

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“Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana.

The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry.

CBD was shown to have anxiolytic, antipsychotic and neuroprotective properties. In addition, basic and clinical investigations on the effects of CBD have been carried out in the context of many other health conditions, including its potential use in epilepsy, substance abuse and dependence, schizophrenia, social phobia, post-traumatic stress, depression, bipolar disorder, sleep disorders, and Parkinson.

CBD is an useful and promising molecule that may help patients with a number of clinical conditions. Controlled clinical trials with different neuropsychiatric populations that are currently under investigation should bring important answers in the near future and support the translation of research findings to clinical settings.”

https://www.ncbi.nlm.nih.gov/pubmed/30298064

https://www.frontiersin.org/articles/10.3389/fimmu.2018.02009/full

A systematic review on the neuroprotective perspectives of beta-caryophyllene.

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“Beta (β)-caryophyllene (BCAR) is a major sesquiterpene of various plant essential oils reported for several important pharmacological activities, including antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, antimicrobial, and immune-modulatory activity. Recent studies suggest that it also possesses neuroprotective effect.

This study reviews published reports pertaining to the neuropharmacological activities of BCAR. Databases such as PubMed, Scopus, MedLine Plus, and Google Scholar with keywords “beta (β)-caryophyllene” and other neurological keywords were searched. Data were extracted by referring to articles with information about the dose or concentration/route of administration, test system, results and discussion, and proposed mechanism of action.

A total of 545 research articles were recorded, and 41 experimental studies were included in this review, after application of exclusion criterion. Search results suggest that BCAR exhibits a protective role in a number of nervous system-related disorders including pain, anxiety, spasm, convulsion, depression, alcoholism, and Alzheimer’s disease.

Additionally, BCAR has local anesthetic-like activity, which could protect the nervous system from oxidative stress and inflammation and can act as an immunomodulatory agent. Most neurological activities of this natural product have been linked with the cannabinoid receptors (CBRs), especially the CB2R. This review suggests a possible application of BCAR as a neuroprotective agent.”

https://www.ncbi.nlm.nih.gov/pubmed/30281175

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934