Abstract Introduction: Chronic pain is the most common reason for medical cannabis certification. Data regarding alcohol use and risky drinking among medical cannabis patients with pain is largely unknown. Therefore, we examined the prevalence and correlates of alcohol use and risky drinking in this population. Methods: Participants completed surveys regarding demographics, pain-related variables, anxiety, cannabis use, and past six-month alcohol consumption. Alcohol use groups were defined using the AUDIT-C [i.e., non-drinkers, low-risk drinkers, and high-risk drinkers (≥4 for men and ≥3 for women)] and compared on demographic characteristics, pain measures, anxiety, and cannabis use. Results: Overall, 42% (n=330/780) were non-drinkers, 32% (n=251/780) were low-risk drinkers, and 26%...

Abstract Medical cannabis has been touted as a solution to the US opioid overdose crisis since Bachhuber et al. [M. A. Bachhuber, B. Saloner, C. O. Cunningham, C. L. Barry, JAMA Intern. Med. 174, 1668–1673] found that from 1999 to 2010 states with medical cannabis laws experienced slower increases in opioid analgesic overdose mortality. That research received substantial attention in the scientific literature and popular press and served as a talking point for the cannabis industry and its advocates, despite caveats from the authors and others to exercise caution when using ecological correlations to draw causal, individual-level conclusions. In this study, we used the same methods...

Abstract Background. The causal impacts of recreational cannabis legalization are not well understood due to the number of potential confounds. We sought to quantify possible causal effects of recreational cannabis legalization on substance use, substance use disorder, and psychosocial functioning, and whether vulnerable individuals are more susceptible to the effects of cannabis legalization than others. Methods. We used a longitudinal, co-twin control design in 4043 twins (N = 240 pairs dis- cordant on residence), first assessed in adolescence and now age 24–49, currently residing in states with different cannabis policies (40% resided in a recreationally legal state). We tested the effect of legalization on...

Abstract   Objectives: To examine the association between Colorado's legalization of recreational cannabis use and opioid-related deaths.   Methods: We used an interrupted time-series design (2000-2015) to compare changes in level and slope of monthly opioid-related deaths before and after Colorado stores began selling recreational cannabis. We also describe the percent change in opioid-related deaths by comparing the unadjusted model-smoothed number of deaths at the end of follow-up with the number of deaths just prior to legalization.   Results: Colorado's legalization of recreational cannabis sales and use resulted in a 0.7 deaths per month (b = -0.68; 95% confidence interval = -1.34, -0.03) reduction in opioid-related deaths....

Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during adolescence on this opiate vulnerability has not been investigated. Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC) exposure during postnatal days 35–49 was made in maternal deprived (D) or non-deprived (animal facility rearing, AFR) rats. The effects of dronabinol exposure were studied after 2 weeks of washout on the rewarding effects of morphine measured in the place preference and oral self-administration tests. The preproenkephalin (PPE) mRNA levels and the relative density and functionality of CB1, and m-opioid receptors were quantified in the striatum and the mesencephalon. Chronic...

Drug addiction is a chronically relapsing disorder characterized by the compulsive desire to use drugs and a loss of control over consumption. Cannabidiol (CBD), the second most abundant component of cannabis, is thought to modulate various neuronal circuits involved in drug addiction. The goal of this systematic review is to summarize the available preclinical and clinical data on the impact of CBD on addictive behaviors. MEDLINE and PubMed were searched for English and French language articles published before 2015. In all, 14 studies were found, 9 of which were conducted on animals and the remaining 5 on humans. A limited number of preclinical studies...

There remains debate regarding the impact of cannabis on neuropsychiatric disorders. Here, we examined the effects of cannabidiol (CBD), a nonpsychoactive constituent of cannabis, on heroin self-administration and drug-seeking behavior using an experimental rat model. CBD (5–20 mg/kg) did not alter stable intake of heroin self-administration, extinction behavior, or drug seeking induced by a heroin prime injection. Instead, it specifically attenuated heroin-seeking behavior reinstated by exposure to a conditioned stimulus cue. CBD had a protracted effect with significance evident after 24 h and even 2 weeks after administration. The behavioral effects were paralleled by neurobiological alterations in the glutamatergic and endocannabinoid systems. Discrete disturbances...

Endocannabinoids and their receptors, mainly the CB1 receptor type, function as a retrograde signaling system in many synapses within the CNS, particularly in GABAergic and glutamatergic synapses. They also play a modulatory function on dopamine (DA) transmission, although CB1 receptors do not appear to be located in dopaminergic terminals, at least in the major brain regions receiving dopaminergic innervation, e.g., the caudate-putamen and the nucleus accumbens/prefrontal cortex. Therefore, the effects of cannabinoids on DA transmission and DA-related behaviors are generally indirect and exerted through the modulation of GABA and glutamate inputs received by dopaminergic neurons. Recent evidence suggest, however, that certain eicosanoid-derived cannabinoids may...

Background: Substitution can be operationalized as the conscious choice to use one drug (legal or illicit) instead of, or in conjunction with, another due to issues such as: perceived safety; level of addiction potential; effectiveness in relieving symptoms; access and level of acceptance. This practice of substitution has been observed among individuals using cannabis for medical purposes. This study examined drug and alcohol use, and the occurrence of substitution among medical cannabis patients. Methods: Anonymous survey data were collected at the Berkeley Patient's Group (BPG), a medical cannabis dispensary in Berkeley, CA. (N = 350) The sample was 68% male, 54% single, 66% White,...

Abstract Binge alcohol consumption in the rat induces substantial neurodegeneration in the hippocampus and entorhinal cortex. Oxidative stress and cytotoxic edema have both been shown to be involved in such neurotoxicity, whereas N-methyl-d-aspartate (NMDA) receptor activity has been implicated in alcohol withdrawal and excitoxic injury. Because the nonpsychoactive cannabinoid cannabidiol (CBD) was previously shown in vitro to prevent glutamate toxicity through its ability to reduce oxidative stress, we evaluated CBD as a neuroprotectant in a rat binge ethanol model. When administered concurrently with binge ethanol exposure, CBD protected against hippocampal and entorhinal cortical neurodegeneration in a dose-dependent manner. Similarly, the common antioxidants butylated hydroxytoluene...