Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation ? Zlebnik NE(1), Cheer JF(1)(2). Author information. Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders Natalie E. Zlebnik .. In contrast to its effects on opioid-motivated behaviors, CBD has .. [ PubMed]; Cheer JF, Marsden CA, Kendall DA, Mason R. Lack of .. [PubMed]; Mechoulam R, Ben-Shabat S, Hanuš L, Ligumsky M, Kaminski NE. PubMed PMID: 7: Zlebnik NE, Cheer JF. Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation? Annu Rev Neurosci.
Receptor: of the NE, Cheer JF. the Disorders CB1 Motivation Answer Zlebnik Cannabidiol for Beyond Is
Antidepressant-like effects were reported in mice following acute or repeated CBD administration in the forced swim [ 7 ] and in the tail suspension tests [ 8 ]. In addition, CBD decreased defensive behaviors evoked by predator exposure, a proposed model of panic attacks and posttraumatic stress disorder PTSD [ 9 , 10 ]. Interestingly, CBD reversed the alteration of prepulse inhibition PPI observed in spontaneously hypertensive rats [ 11 ] and in a glutamate-based models of psychosis [ 12 ] and exhibited a similar profile compared with atypical antipsychotic drugs [ 13 , 14 ].
Indeed, CBD improved cognition in several preclinical models of cognitive impairment [ 15 ]. CBD reduced heroin craving and relapse [ 16 ], and cocaine [ 17 ] and alcohol consumption mice [ 18 ]. In spite of the number of findings suggesting the potential therapeutic use of CBD, there is some controversy regarding its profile as a drug of abuse that significantly hampers further development of basic and clinical studies.
However, there is no evidence that supports these considerations. On the other hand, CBD is not under any special restrictions in Europe. The lack of psychoactive activity appears to be related with its low affinity on CB1 receptors fold less than THC [ 33 ]. Interestingly, recent studies carried out in our laboratory demonstrated that CBD did not induce conditioned-place preference, withdrawal signs or oral self-administration suggesting lack of properties as a drug of abuse [ 34 ]. Responding during signaled availability and nonavailability of iv cocaine and food in rats: Beyond the CB1 receptor: Differential effects of allopregnanolone on the escalation of cocaine self-administration and sucrose intake in female rats JJ Anker, NE Zlebnik, ME Carroll Psychopharmacology 3 , , Effects of the combination of wheel running and atomoxetine on cue-and cocaine-primed reinstatement in rats selected for high or low impulsivity NE Zlebnik, ME Carroll Psychopharmacology 6 , , Drug-induced alterations of endocannabinoid-mediated plasticity in brain reward regions NE Zlebnik, JF Cheer Journal of Neuroscience 36 40 , , Cocaine-, caffeine-, and stress-evoked cocaine reinstatement in high vs.
Prevention of the incubation of cocaine seeking by aerobic exercise in female rats NE Zlebnik, ME Carroll Psychopharmacology 19 , , Each item is rated 0 to 3 and yields a total score from 0 to A higher number indicates more sleep-related concerns. Side effects and tolerability of CBD treatment were assessed through spontaneous patient self-reports and were documented in case records. Any other spontaneous comments or complaints of patients were also documented in case records and included in this analysis.
Deidentified patient data were evaluated using descriptive statistics and plotted graphically for visual analysis and interpretation of trends. Most patients with an anxiety diagnosis were men All 72 patients completed sleep and anxiety assessments at the onset of CBD treatment and at the first monthly follow-up.
By the second monthly follow-up, 41 patients On average, anxiety and sleep improved for most patients, and these improvements were sustained over time. At the first monthly assessment after the start of CBD treatment, Two months after the start of CBD treatment, These results demonstrated a more sustained response to anxiety than for sleep over time.
Patient records displayed a larger decrease in anxiety scores than in sleep scores. The sleep scores demonstrated mild improvement.
The anxiety scores decreased within the first month and then remained decreased during the study duration. CBD was well tolerated, with few patients reporting side effects. Two patients discontinued treatment within the first week because of fatigue. Three patients noted mild sedation initially that appeared to abate in the first few weeks. One patient with a developmental disorder aged 21 years had to be taken off the CBD regimen because of increased sexually inappropriate behavior. The CBD was held, and the behavior disappeared.
The behavior reappeared on redosing 2 weeks later, and the CBD regimen was formally discontinued. One patient noted dry eyes. Reasons for patients not following-up at later assessment points are largely unknown but are probably because of standard attrition experienced in usual clinical practice. There was no evidence to suggest patients discontinued care because of tolerability concerns.
The attrition rates were similar in nature and size to those found in routinely scheduled visits in this clinic. Four patients declined CBD treatment because of religious or ethical concerns about the relation to cannabis. Nearly all patients easily provided informed consent once the nature of the treatment was explained. Most patients appreciated the opportunity to try something natural and avoid further or initial psychiatric medication use.
In an outpatient psychiatric population, sleep scores displayed no sustained improvements during the 3-month study. Anxiety scores decreased fairly rapidly, and this decrease was sustained during the study period.
These results are consistent with the existing preclinical and clinical data on CBD. CBD was well accepted and well tolerated in our patients. Side effects were minimal mainly fatigue and may be related to dosing. The first is that in our experience lower doses appear to elicit an adequate clinical response.
These results must be interpreted cautiously because this was a naturalistic study, all patients were receiving open-label treatment, and there was no comparison group.
Concurrent psychiatric medications were employed as in routine clinical care. This is both a limitation and strength, as very few publications exist in this population. Other researchers have noted that the large societal notoriety about cannabis and medical marijuana probably contributes to a larger-than-normal placebo effect.
Likewise, the clinical population in this case series is skewed younger than typical for our clinic, and future studies could explore the possible selection bias inherent in this treatment option. Most patients were also taking psychiatric medications and receiving other mental health services, such as counseling, which limits the ability to make any causal links to CBD treatment. Clinical attrition is evident in the dataset. The reason for this might be related to CBD ingestion or not, so the overall component remains unclear.
Furthermore, patients at our clinic often express a desire to reduce or to avoid use of psychiatric medications, which may contribute to an enhanced placebo effect or additional bias. The length of clinical monitoring may help to decrease this concern. However, the clinical data in this analysis show a trend toward clinically significant relief of anxiety upon the start of CBD treatment.
The legality of CBD is not clear. Like the issues surrounding the legality of cannabis in general, CBD presents the clinician with a confusing state vs federal legal quandary, and this keeps the issue in question.
The federal government has announced that it is not focused on this compound in terms of enforcement or interdiction.
Pending federal legislation to redefine the legal status of cannabis would clarify this complex issue. Formal studies on efficacy and dose finding are much needed. Some urgency exists, given the explosion of lay interest in this topic and the rush to market these compounds.
Current understanding of the physiology and neurologic pathways points to a benefit with anxiety-related issues. The results of our clinical report support the existing scientific evidence. In our study, we saw no evidence of a safety issue that would limit future studies.
In this evaluation, CBD appears to be better tolerated than routine psychiatric medications. Furthermore, CBD displays promise as a tool for reducing anxiety in clinical populations, but given the open-label and nonrandomized nature of this large case series, all results must be interpreted very cautiously. Randomized and controlled trials are needed to provide definitive clinical guidance. Dr Shannon has published several professional books on integrative mental health.
Dr Shannon is a Principal Investigator for a Phase 3 study of 3,4-methylenedioxy-methamphetamine MDMA -assisted psychotherapy for severe posttraumatic stress disorder and receives compensation for his clinical work from the Multidisciplinary Association for Psychedelic Studies, Santa Cruz, CA. The other authors have no conflicts of interests to disclose. CV Sciences was not involved in the data collection, data interpretation, preparation of the report, or decision to submit the report for publication.
Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?
Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation ? Zlebnik, N.E.; Cheer, J.F.. Annual Review of Neuroscience Agonistic properties of cannabidiol at 5-HT1a receptors. Zlebnik NE, Cheer JF. Beyond the CB1 receptor: is Cannabidiol the answer for disorders of motivation. , Covey DP, Dantrassy HM, Zlebnik NE, Gildish I, Cheer JF. Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation? of conditioned stimuli Cannabinoid Modulation of Emotion, Memory, and Motivation.