Illness: Facts and Unanswered Questions Michael S. Shafer, PhD; - - PowerPoint PPT Presentation
Summer Institute 2014 Medical Cannabis Use Among Individuals Experiencing Mental Illness: Facts and Unanswered Questions Michael S. Shafer, PhD; Harrison Stratton, PhD Candidate, Neuroscience; Jessica Mueller, Christine Phillips, PhD;
Summer Institute 2014
Michael S. Shafer, PhD; Harrison Stratton, PhD Candidate, Neuroscience; Jessica Mueller, Christine Phillips, PhD; Richard Rivera, MS; Beth Hartman Ellis, PhD; Erica Davis,
I. The Human Endogenous Cannabinoid System (ECS) II. Medical Cannabis and Mental Illness III. Dispensary Patient Survey IV. Issues and Implications for the Behavioral Health Providers
GPR55 and GPR18
CB receptor localization. CB receptors are found in the basal ganglia, cerebellum, hippocampus & throughout the cerebral cortex.
Retrograde signaling through the release of 2-AG at glutamatergic and GABAergic synapses. 2-AG is synthesized by the post-synaptic cell and diffuses through the synaptic cleft where it can bind to CB receptors at the presynaptic terminal. Activation of CB receptors can produce either transient or prolonged inhibition (GLU) or disinhibition (GABA).
The ECS regulates homeostatic mechanisms and immunity
Tegmental Area, Nucleus Accumbens, and Hippocampus
The ECS has the potential to modulate a variety of subsystems
Anecdotal, human, and animal studies have all suggested a plausible role for THC and other cannabinoids in depression and anxiety specifically
– Potential for patients to grow their own medicine
Drug discovery techniques have provided a large variety of “cannabino-mimetic” molecules (i.e. JWH-133)
Alterations in the eCB system appear to play a key role in mood disorders. Reduced functionality might be considered a predisposing factor for major depression, so boosting the eCB tone might be a useful alternative therapeutic approach for depressive disorder.
Parolaro,D., Realini,N.,Vigano,D.,Guidali,C.,Rubino,T.(2010). The encocannabinoid system and psychiatric disorders. Experimental Neurology, 224, 3-10.
The picture regarding eCBs and anxiety is more complicated since either too much or too little AEA can lead to anxiety
might be beneficial for the response to a stressful situation and therefore to tone down anxiety. Based on this last assumption, a slight increase in eCB tone
indirect agonists, such as blockers of the degradative pathway (i.e. FAAH) or re-uptake inhibitors.
Parolaro,D., Realini,N.,Vigano,D.,Guidali,C.,Rubino,T.(2010). The encocannabinoid system and psychiatric disorders. Experimental Neurology, 224, 3-10.
Fairly consistent reporting of medical cannabis users and other cannabis users substituting cannabis for other substances, including prescription medications, alcohol, & illicit drugs Dispensary patients cite less adverse side effects, better symptom management, and less withdrawal potential as reasons for substituting cannabis for other prescription medications. Some anecdotal and case study reports of the utilization of medical cannabis as a harm reduction intervention among methamphetamine users, and other illicit substance abuse individuals.
…in individuals with a predisposition for schizophrenia, the ingestion of cannabis exacerbates symptoms and worsens the schizophrenic prognosis. In addition to cannabis producing acute psychotic like symptoms, epidemiological data suggests that cannabis is a risk factor for the onset of schizophrenia. The risk
manner with increasing frequency of cannabis use and when cannabis is used in adolescence…. …..Concerning the potentiality of the pharmacological manipulation of the eCB system as a novel approach for treating schizophrenia, the experimental findings are still controversial, often with different effects depending
negative symptoms.
Parolaro,D., Realini,N.,Vigano,D.,Guidali,C.,Rubino,T.(2010). The encocannabinoid system and psychiatric disorders. Experimental Neurology, 224, 3-10.
Research Questions: 1. What is the prevalence of mental health diagnoses in cannabis dispensary patients? 2. What are dispensary patients’ reported patterns of cannabis use and psychological treatment? 3. What are the reported patterns of medical cannabis use between individuals with psychiatric diagnoses and those without?
with patients.
ADHS Report (July 2014) CABHP Sample (December 2013-January 2014)
19.7% 31 to 40 years of age (mean age not available)
available
available
63% 28% 14% 7% 2% 1% 3%
0% 10% 20% 30% 40% 50% 60% 70% None Generalized Anxiety Disorder Major Depressive Disorder Bipolar Disorder Personality Disorder Psychotic Disorder Other
Have you been told by a health professional, such as a psychologist, psychiatrist, physician or other health provider that you currently have any
(diagnosed responses not mutually exclusive; N=483)
Major Depressive Disorder Generalized Anxiety Disorder No reported mental disorder Other Bipolar Disorder Psychotic Disorder Personality Disorder
9% report current mental health treatment 20% report past mental health treatment
51% 24% 15% 10% 45% 24% 20% 11% 0% 10% 20% 30% 40% 50% 60% 1 to 3 3 to 5 5 to 7 Over 7 No MH Dx MX Dx Frequency of Daily Use of Medical Cannabis 0% 10% 20% 30% No MH Dx MH Dx 22% 27% CAGE Clinical Significance
2.6 2.7 2.8 2.9 3 3.1 3.2 3.3 No MH Dx MH Dx 2.87 3.26
Pain Interference
Your job just got harder! Therapeutic use vs. illegal and abusive use Integrating medical cannabis use and psychotropic medications Managing substance abuse patients and drug court referrals and CJ system involved clients Medical cannabis diversion
Prescriptive Taxonomy
– Patient profiling – Dosing – Medicine assaying & chemical composition
Clinical Information Needs
– Clinical trials efficacy focused – Health literacy – Quality standards
Policy Information Needs
– Provider control and oversight – Fee & tax revenue models – Public safety and crime prevention
“…as physicians know how to do with gauging patients' consumption of alcohol, nicotine and various opiate preparations, they should demand and expect honesty of their patients, take histories of their cannabis ingestion, monitor for signs of pathological use, discuss the risks and benefits with them and counsel them from a stance of knowledge and respect about curtailing problematic consumption.”
Bpstwick,J.M. (2014). The use of cannabis for management of chronic pain. General Hospital Psychiatry, 36,2-3.
Agudo J, Martin M, Roca C, Molas M, Bura AS, Zimmer A, Bosch F, Maldonado R. Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age. " Diabetología2010; Sep 11. Benito C, Tolón RM, Pazos MR, Núñez E, Castillo AI, Romero J. Cannabinoid CB2 receptors in human brain inflammation.British Journal of Pharmacology. 2008;153:277-285. Deutsch DG, Chin SA. Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor
Felder CC, Glass M. Cannabinoid receptors and their endogenous agonists. Annual review of pharmacology and
Hill MN, McEwen BS, McLaughlin RJ, et al. Endogenous cannabinoid signaling is essential for stress adaptation.Proceedings of the National Academy of Sciences of the United States of America. 2010;107:9406- 9411. Maccarrone M, Finazzi-Agró A. The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis.Cell death and differentiation. 2003;10:946-955. Pertwee RG. Ligands that target cannabinoid receptors in the brain: from THC to anandamide and
Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarin. British Journal of Pharmacology. 2008;153:199-215. Piomelli D. The molecular logic of endocannabinoid signalling.Nature reviews. Neuroscience. 2003;4:873-884.