Category Archives: Addiction

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

Repeated Cannabidiol treatment reduces cocaine intake and modulates neural proliferation and CB1R expression in the mouse hippocampus.

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Neuropharmacology

“Cannabinoid derivatives have shown promising results for treating neuropsychiatric disorders, including drug addiction.

Recent studies on the therapeutic effects of Cannabidiol (CBD) on drug abuse showed mixed results, especially with psychostimulant substances such as cocaine. To determine whether CBD can attenuate cocaine reinforcement, we assessed behavioural responses induced by cocaine in mice, using the behavioural sensitization, conditioned place preference and intravenous self-administration paradigms.

We show that repeated CBD treatment produces anxiolytic effects in the elevated plus maze test, increases the discrimination index of the novel object recognition task and attenuates cocaine-induced conditioned place preference but does not affect behavioural sensitization.

CBD reduced cocaine voluntary consumption and progressive ratio breaking point in the self-administration paradigm, but not drug-induced reinstatement. In parallel, CBD increased expression of type 1 cannabinoid receptor, MAPK-CREB phosphorylation, BDNF expression, and neural cell proliferation in the hippocampus, and reduced the GluA1/2 AMPA subunit receptor ratio in the striatum.

In summary, we show that CBD can modulate some behavioural and molecular manifestations of cocaine reinforcement. Moreover, our findings show that CBD has pro-neurogenic effects also in cocaine consuming animals.

Overall, this novel evidence provides new perspectives to use CBD as a therapeutic tool.”

https://www.ncbi.nlm.nih.gov/pubmed/30273593

https://www.sciencedirect.com/science/article/pii/S0028390818307135?via%3Dihub

Cannabidiol treatment reduces the motivation to self-administer methamphetamine and methamphetamine-primed relapse in rats.

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“Methamphetamine is an addictive stimulant that can cause many adverse physical, psychological and psychosocial effects.

Preliminary evidence shows cannabidiol, a non-intoxicating constituent of the cannabis plant, may have efficacy in treating opioid and nicotine dependence. However, no study has yet examined whether cannabidiol treatment might impact on methamphetamine addiction.

AIMS:

The current study investigated whether cannabidiol administration reduces the motivation to self-administer methamphetamine and relapse to methamphetamine-seeking behavior following abstinence.

RESULTS:

Cannabidiol (80 mg/kg, but not 40 mg/kg, or 20 mg/kg) reduced the motivation to self-administer methamphetamine and attenuated methamphetamine-primed relapse to methamphetamine-seeking behavior after extinction.

CONCLUSION:

This is the first demonstration that cannabidiol can reduce the motivation to seek and consume methamphetamine, and suggests that cannabidiol might be worth trialing as a novel pharmacotherapy for methamphetamine dependence.”

https://www.ncbi.nlm.nih.gov/pubmed/30260267

http://journals.sagepub.com/doi/abs/10.1177/0269881118799954?journalCode=jopa

Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle.

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“Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders. Recently, CBD has also been explored for potential in treating drug addiction.

Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control.

Here, we evaluated the “anti-relapse” potential of a transdermal CBD preparation in animal models of drug seeking, anxiety and impulsivity.

The results provide proof of principle supporting potential of CBD in relapse prevention along two dimensions: beneficial actions across several vulnerability states and long-lasting effects with only brief treatment.

The findings also inform the ongoing medical marijuana debate concerning medical benefits of non-psychoactive cannabinoids and their promise for development and use as therapeutics.”

https://www.ncbi.nlm.nih.gov/pubmed/29686308

https://www.nature.com/articles/s41386-018-0050-8

“Unique treatment potential of cannabidiol for the prevention of relapse to drug use” https://www.nature.com/articles/s41386-018-0218-2