Medical Marijuana A Primer for Pharmacists

Transcription

1 Medical Marijuana A Primer for Pharmacists Emory S. Martin, PharmD FASHP Texas Society of Health System Pharmacists Learning Objectives Recognize key components of the endocannabinoid system Identify possible roles of plant or pharmaceutical cannabinoids in therapy of disease Explain the current evidence-based place in therapy of cannabinoids Explain today s medical-legal status 2 The Endocannabinoid System 3 1

2 Arachidonic acid compounds! 4 N arachidonoyl phosphatidyl ethanol (NAPE) AEA Biosynthesis Start Here Precursors for EC found in lipid membranes Rapidly synthesized on demand; not stored Similar to a neurotransmitter, released from neurons after membrane depolarization Biological Psychiatry April 1, 2016; 79: AG Biosynthesis Start Here 2 AG is also: an important intermediate in lipid synthesis & serves as a major source of AA in prostaglandin synthesis arachidonoyl-containing phosphatidyl inositol bis-phosphate Lu & Mackie. Biological Psychiatry April 1, 2016; 79:

3 Next A cursory review of neuroanatomy! 7 Reminiscent of μ receptors - in the thalamus, amygdala and other brain regions involved in pain but ALSO other physiological functions including respiratory and CV functions, intestinal transit, feeding, mood, thermoregulation, hormone secretion and immune functions

4 Lu & Mackie. Biological Psychiatry April 1, 2016; 79: Ligand Activity at CB1 & CB2 Receptors Endogenous Ligands (endocannabinoids) AEA 2-AG Plant Origin Ligands (phytocannabinoids) Tetrahydrocannabinol (THC, Δ 9 -THC) Cannabidiol (CBD) >60 related cannabinoid compounds Atakan. Ther Adv Psychopharmacol Dec; 2(6): Receptors in Humans CB1 (CNS) Receptors 2-AG strong agonist AEA weak agonist (partial) THC weak agonist (partial); still strongly psychoactive CBD very weak agonist; non-psychoactive CB2 (Peripheral) Receptors 2-AG strong agonist AEA very weak agonist; little activity THC very weak agonist; little activity CBD agonist Animal data does not correlate well CBD modifies the effect of THC and may reduce the anxiety, psychosis and memory impairment provoked by THC. 12 4

5 True or False Assessment! 1. As you sit here listening, you may have EC acting at multiple CNS and peripheral NS sites impacting your appetite, mood, thought process, and memory. 2. PhytoCB interact with receptors differently than EC. 3. The primary effect of THC is altered cognition and euphoria, but there may be more subtle effects. 4. CBD may have more effects in the periphery and may moderate THC effects in the CNS. 5. Mother s milk contains EC which apparently encourages feeding. 13 Cannabis Plant Species Cannabis sativa THC >CBD Cannabis indica CBD >THC Hybrids of the two Hybrids of the hybrids Most of the marijuana sold illegally in the United States contains no cannabidiol or very low amounts of it, and the THC levels of marijuana may vary from about 3 to 25% (to increase the high ). 14 Cannabinoids in Other Plant Species? Echinacea (Cone flower): N-alkylamide (cannabimimetic) Ruta graveolens L (Rue)- Rutamarin Acmella oleracea (Electric daisy, toothache plant) - N- Isobutylamides Theobroma cacao (Chocolate) -anandamide and 2 other compounds + inhibitor of EC breakdown Misc. plants - β-caryophyllene

6 Vaping 16 Medical Cannabinoids 17 Cannabis Herbs & Extracts 18 6

7 Commercial dispensers promote tailored therapy in so many indications 19 Pharmaceutical Cannabinoids 20 Approved Indications 21 7

8 Synthetics 22 Not Including the Hallucinogen Spice (K2) HU-210, HU-211, JWH-018, and JWH True or False Assessment! 1. FDA-approved uses of PharmCB include, anorexia, weight gain in AIDS, N/V in cancer and seizures associated with MS 2. Possible (purported) medical uses of CB are in the thousands 3. Forms of CB being formally tested include Cannabis flowers and leaves, extracts from Cannabis, synthetic versions of PhytoCB, other synthetic CB s including K2 24 8

9 Anecdotal Evidence, Case Reports, Open Label Studies, RCT >23,000 reports dealing with therapeutic use of CBs published 25 Major Meta Analysis JAMA. 2015;313(24): doi: /jama Study Selection 27 9

10 Included Compounds Smoked or Vaped Cannabis Cannabidiol (CBD) Extracted THC Combination of THC and CBD Dronabinol capsules Levonantradol (PO or IM) Nabilone capsules Nabixmols spray Ajulemic Acid (CT-3) 28 Typical Adult Doses 29 Efficacy Results 30 10

11 AE Results 31 Efficacy in Cancer N/V 32 Individual Trials 33 11

12 Efficacy in Weight Maintenance 34 Efficacy in Weight Maintenance 35 Efficacy in Seizure Prevention 36 12

13 CBD in Seizure Prevention 37 ADHD Postulate: In certain patients, suboptimal EC levels in the CNS may allow excessive speeds neurotransmitter functions May produce rapid thoughts Theory: Inhibition of the metabolic breakdown of EC or supplementation with exogenous CB may slow down thought process Anecdotal reports of improved academic performance in school David Bearman, M.D., Cannabis Researcher interview 38 RCT (Pilot) Abstract King s College, UK, ADHD patients SATIVEX spray vs placebo Good trend in improved cognition and behavior 39 13

14 True or False Assessment! 1. The best scientific evidence for possible new indications for CB include chronic neuropathic pain and cancer pain 2. There is some evidence (but weaker) for a role in sleep disorders, Turette s syndrome, and certain types of seizures in children. 3. A recent UK RCT in ADHD showed a trend toward improvement in certain ADHD behavioral tests 40 Legal Status Across U.S. 41 Texas Legal Status 42 14

15 Recent Changes 43 Texas CBD Oil 2017 CBS concentrate oils must contain at least 10 percent CBD, and not more than 0.5 percent THC. Texas DPS will issue up to 3 licenses by April 30, 2017 DPS has floated a proposal to raise license fee from $6000 to 1.3 million, but settled on $7356 app fee, + $488K/2 yr 24 /7 trooper on site? 1 group in Gunter (North Texas) plans to apply for license to dispense Some town residents are having a fit CBD Oil In Texas

16 Where We Are Today The results of studies with individual cannabinoids (eg, THC or CBD) cannot be extrapolated to marijuana and vice versa.... for most qualifying conditions (listed in various states laws), approval has relied on low-quality scientific evidence, anecdotal reports, individual testimonials, legislative initiatives, and public opinion. Imagine if other drugs were approved through a similar approach. 46 Significant Issues Approximately 1 in 10 adult users of marijuana develops addiction - higher among adolescents. Repeated use long term increases the risk of psychosis in some sub-groups Contraindication in schizophrenia, bipolar disorder, or substance dependence? CBD oil as a legal gateway to broader access We didn t serve the public with overprescribing of opiates 47 Where We Are Today It is only by the process of science guided by rational and ethical advocacy for the best interest of the patient that we will come to an answer and not leave people to their own devices. Hopefully, there will be less polarity, less politicization of this issue, and more focus on what is real and what is not Editorial: Sirvin JI. Medical marijuana for epilepsy: Winds of change 48 16

17 True or False Assessment! 1. Texas has recently relaxed marijuana laws 2. Medicinal use of CB is code for clandestine recreational use. 3. All opioid use is evil; All CB use is evil 4. All opioid use is good; All CB use is good