Preclinical Studies of Cannabinoid Reward, Treatments for Cannabis Use Disorder, and Addiction-Related Effects of Cannabinoid Exposure

Panlilio, Leigh V.; Justinová, Zuzana

doi:10.1038/npp.2017.193

Cited by 31 publications

(21 citation statements)

References 252 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the tools do not currently exist to selectively manipulate CB 1 Rs in a terminal-specific manner in the VTA, future studies should investigate whether these VTA cell type-specific changes in CB 1 R levels are sufficient to drive acute responses to THC-and reward-related behaviors, as well as the higher THC-induced c-Fos levels observed in the NAc of FAAH C/A mice. Contexts associated with initiation of drug use can precipitate drug craving and contribute significantly to drug dependence (35). For example, social contexts, such as the presence of peers, can considerably influence the addictive process particularly in adolescence and predict the initiation and maintenance of drug use (36).…”

Section: Discussionmentioning

confidence: 99%

Endocannabinoid genetic variation enhances vulnerability to THC reward in adolescent female mice

et al. 2020

View full text Add to dashboard Cite

Adolescence represents a developmental period with the highest risk for initiating cannabis use. Little is known about whether genetic variation in the endocannabinoid system alters mesolimbic reward circuitry to produce vulnerability to the rewarding properties of the exogenous cannabinoid Δ9-tetrahydrocannabinol (THC). Using a genetic knock-in mouse model (FAAHC/A) that biologically recapitulates the human polymorphism associated with problematic drug use, we find that in adolescent female mice, but not male mice, this FAAH polymorphism enhances the mesolimbic dopamine circuitry projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and alters cannabinoid receptor 1 (CB1R) levels at inhibitory and excitatory terminals in the VTA. These developmental changes collectively increase vulnerability of adolescent female FAAHC/A mice to THC preference that persists into adulthood. Together, these findings suggest that this endocannabinoid genetic variant is a contributing factor for increased susceptibility to cannabis dependence in adolescent females.

show abstract

Section: Discussionmentioning

confidence: 99%

Endocannabinoid genetic variation enhances vulnerability to THC reward in adolescent female mice

et al. 2020

View full text Add to dashboard Cite

show abstract

“…There is also evidence that some of the behavioral and downstream neurobiological effects of Δ9-THC are partially shared with MOP-r systems ( 25 , 61 ). Preclinical studies show that the amount and pattern of exposure to specific drugs of abuse are critical in the emergence of underlying neurobiological changes and of addiction-like behaviors ( 62 – 65 ). Overall, substantial non-medical cannabis exposure in adolescence and early adulthood may result in long-lasting disruption in these and other systems, and thus result in increased vulnerability to the later development of opioid use disorders.…”

Section: Discussionmentioning

confidence: 99%

Non-medical Cannabis Self-Exposure as a Dimensional Predictor of Opioid Dependence Diagnosis: A Propensity Score Matched Analysis

et al. 2018

View full text Add to dashboard Cite

Background: The impact of increasing non-medical cannabis use on vulnerability to develop opioid use disorders has received considerable attention, with contrasting findings. A dimensional analysis of self-exposure to cannabis and other drugs, in individuals with and without opioid dependence (OD) diagnoses, may clarify this issue.Objective: To examine the age of onset of maximal self-exposure to cannabis, alcohol, cocaine, and heroin, in volunteers diagnosed with OD, using a rapidly administered instrument (the KMSK scales). To then determine whether maximal self-exposure to cannabis, alcohol, and cocaine is a dimensional predictor of odds of OD diagnoses.Methods: This outpatient observational study examined maximal self-exposure to these drugs, in volunteers diagnosed with DSM-IV OD or other drug diagnoses, and normal volunteers. In order to focus more directly on opioid dependence diagnosis as the outcome, volunteers who had cocaine dependence diagnoses were excluded. Male and female adults of diverse ethnicity were consecutively ascertained from the community, and from local drug treatment programs, in 2002–2013 (n = 574, of whom n = 94 had OD diagnoses). The age of onset of maximal self-exposure of these drugs was examined. After propensity score matching for age at ascertainment, gender, and ethnicity, a multiple logistic regression examined how increasing self-exposure to non-medical cannabis, alcohol and cocaine affected odds of OD diagnoses.Results: Volunteers with OD diagnoses had the onset of heaviest use of cannabis in the approximate transition between adolescence and adulthood (mean age = 18.9 years), and onset of heaviest use of alcohol soon thereafter (mean age = 20.1 years). Onset of heaviest use of heroin and cocaine was detected later in the lifespan (mean ages = 24.7 and 25.3 years, respectively). After propensity score matching for demographic variables, we found that the maximal self-exposure to cannabis and cocaine, but not to alcohol, was greater in volunteers with OD diagnoses, than in those without this diagnosis. Also, a multiple logistic regression detected that increasing self-exposure to cannabis and cocaine, but not alcohol, was a positive predictor of OD diagnosis.Conclusions/Importance: Increasing self-exposure to non-medical cannabis, as measured with a rapid dimensional instrument, was a predictor of greater odds of opioid dependence diagnosis, in propensity score-matched samples.

show abstract

“…Despite their ability to evoke NAc DA release (Wise and Bozarth 1987;Koob 1992;Tanda et al 1997;Oleson and Cheer 2012), and their voluntary use in humans, there has been considerable difficulty in developing reliable rodent models of cannabinoid selfadministration (Justinova et al 2005;Panlilio and Justinova 2018). Although, as has been suggested, the lack of solubility of these hydrophobic compounds and other pharmacodynamic issues may limit their efficacy in these models (Melis et al 2017), we propose that the ability of cannabinoids to act to disrupt the function of widespread neural networks may also contribute to this problem.…”

Section: Dysfunction Of Da and Cortical Circuitry Following Long-termmentioning

confidence: 92%

Cannabinoid disruption of learning mechanisms involved in reward processing

Lupica

Hoffman

2018

Learn. Mem.

View full text Add to dashboard Cite

The increasing use of cannabis, its derivatives, and synthetic cannabinoids for medicinal and recreational purposes has led to burgeoning interest in understanding the addictive potential of this class of molecules. It is estimated that ∼10% of marijuana users will eventually show signs of dependence on the drug, and the diagnosis of cannabis use disorder (CUD) is increasing in the United States. The molecule that sustains the use of cannabis is Δ-tetrahydrocannabinol (Δ-THC), and our knowledge of its effects, and those of other cannabinoids on brain function has expanded rapidly in the past two decades. Additionally, the identification of endogenous cannabinoid (endocannabinoid) systems in brain and their roles in physiology and behavior, demonstrate extensive involvement of these lipid signaling molecules in regulating CNS function. Here, we examine roles for endogenous cannabinoids in shaping synaptic activity in cortical and subcortical brain circuits, and we discuss mechanisms in which exogenous cannabinoids, such as Δ-THC, interact with endocannabinoid systems to disrupt neuronal network oscillations. We then explore how perturbation of the interaction of this activity within brain reward circuits may lead to impaired learning. Finally, we propose that disruption of cellular plasticity mechanisms by exogenous cannabinoids in cortical and subcortical circuits may explain the difficulty in establishing viable cannabinoid self-administration models in animals.

show abstract

Preclinical Studies of Cannabinoid Reward, Treatments for Cannabis Use Disorder, and Addiction-Related Effects of Cannabinoid Exposure

Cited by 31 publications

References 252 publications

Endocannabinoid genetic variation enhances vulnerability to THC reward in adolescent female mice

Endocannabinoid genetic variation enhances vulnerability to THC reward in adolescent female mice

Non-medical Cannabis Self-Exposure as a Dimensional Predictor of Opioid Dependence Diagnosis: A Propensity Score Matched Analysis

Cannabinoid disruption of learning mechanisms involved in reward processing

Contact Info

Product

Resources

About