Objective To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regards to their relevance to epilepsy and other selected neuropsychiatric disorders. Methods We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology and data from studies with animal models and human subjects. Results Cannabis has been used to treat disease since ancient times. Δ9-THC is the major psychoactive ingredient and cannabidiol (CBD) is the major non-psychoactive ingredient in cannabis. Cannabis and Δ9-THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. Psychotropic effects of Δ9-THC limit tolerability. CBD is anticonvulsant in many acute animal models but there is limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of melastatin type 8 channel; the 5-HT1a receptor; the α3 and α1 glycine receptors; and the transient receptor potential of ankyrin type 1 channel. CBD has neuroprotective and anti-inflammatory effects. CBD appears to be well tolerated in humans but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:Δ9-THC medical marijuana have claimed efficacy, but studies were not controlled. Significance CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted.

Aims: The study objectives were to examine trends in prescription opioid (PO) injection and to assess its association with HCV seroconversion among injection drug users (IDUs), accounting for other risk factors.Design and Setting: A prospective cohort study of IDUs was carried out between 2004 and 2009 in Montreal, Canada.Participants and Measurements: 246 HCV-negative IDUs were included in this analysis. Semiannual visits included HCV antibody testing and an interview-administered questionnaire assessing risk behaviours. HCV incidence rate was calculated using the person-time method.Time-updated Cox regression models were conducted to examine predictors of HCV incidence.Findings: The proportion of IDUs reporting PO injection increased from 21% to 75% between 2004 and 2009 (p < 0.001). Of the 246 participants (81.6% male; mean age 34.5 years; mean follow-up time 23 months), 83 seroconverted to HCV (incidence rate: 17.9 per 100 person-years; 95% CI 14.3, 22.1). PO injectors were more likely to become infected if they did not use injection heroin (Adjusted Hazard Ratio (AHR): 2.9 (95% CI: 1.5, 5.5)), whereas the association was not statistically significant for participants who reported using both drugs (AHR: 1.2 (95%CI: 0.6, 2.3). Other independent predictors of HCV incidence were: cocaine injection, recent incarceration, and > 30 injections per month.Conclusion: PO injection has increased rapidly in recent years, and appears to be an important risk factor for HCV acquisition. Our results suggest that the risks related to PO injection may be conditioned by specific drug practices which differ from those of heroin users.

Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ 9 -tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from Bmedical CBD^and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant.

Despite the high prevalence of marijuana use among pregnant women and adolescents, the impact of cannabis on the developing brain is still not well understood. However, growing evidence supports that the endocannabinoid system plays a major role in CNS patterning in structures relevant for mood, cognition, and reward, such as the mesocorticolimbic system. It is thus clear that exposure to cannabis during early ontogeny is not benign and potential compensatory mechanisms that might be expected to occur during neurodevelopment appear insufficient to eliminate vulnerability to neuropsychiatric disorders in certain individuals. Both human longitudinal cohort studies and animal models strongly emphasize the long-term influence of prenatal cannabinoid exposure on behavior and mental health. This review provides an overview of the endocannabinoid system and examines the neurobiological consequences of cannabis exposure in pregnancy and early life by addressing its impact on the development of neurotransmitters systems relevant to neuropsychiatric disorders and its association with these disorders later in life. It posits that studying in utero cannabis exposure in association with genetic mutations of neural systems that have strong relationships to endocannabinoid function, such as the dopamine, opioid, glutamate, and GABA, might help to identify individuals at risk. Such data could add to existing knowledge to guide public health platform in regard to the use of cannabis and its derivatives during pregnancy.

Objectives Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods This double-blind, placebo-controlled cross-over study of CBD co-administered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21–65 years with prior opioid exposure, regardless of route. Blood samples were obtained before and after 400 or 800 mg CBD pretreatment, followed by a single 0.5 (Session 1) or 1.0mcg/Kg (Session 2) intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. Results SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. Following low dose CBD, tmax occurred at 3 and 1.5h (Sessions 1 and 2, respectively). Following high dose CBD, tmax occurred at 3 and 4h in Sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC p=NS) between sessions. Conclusions CBD does not exacerbate adverse effects associated with intravenous fentanyl administration. Co-administration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse.

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 suggest that CBD may have therapeutic properties on opioid, cocaine, and psychostimulant addiction, and some preliminary data suggest that it may be beneficial in cannabis and tobacco addiction in humans. Further studies are clearly necessary to fully evaluate the potential of CBD as an intervention for addictive disorders.

The adolescent brain is a period of dynamic development making it vulnerable to environmental factors such as drug exposure. Of the illicit drugs, cannabis is most used by teenagers since it is perceived by many to be of little harm. This perception has led to a growing number of states approving its legalization and increased accessibility. Most of the debates and ensuing policies regarding cannabis were done without consideration of its impact on one of the most vulnerable population, namely teens, or without consideration of scientific data. We provide an overview of the endocannabinoid system in relation to adolescent cannabis exposure and provide insights regarding factors such as genetics and behavioral traits that confer risk for subsequent addiction. While it is clear that more systematic scientific studies are needed to understand the long-term impact of adolescent cannabis exposure on brain and behavior, the current evidence suggests that it has a far-reaching influence on adult addictive behaviors particularly for certain subsets of vulnerable individuals.

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