Medical Marijuana What s the Buzz? THC vs CBD? Alan Kaplan MD CCFP(EM) FCFP Pain Consultant

Transcription

1 Medical Marijuana What s the Buzz? THC vs CBD? Alan Kaplan MD CCFP(EM) FCFP Pain Consultant

2 Faculty/Presenter Disclosure Faculty: Alan Kaplan MD CCFP(EM) FCFP Chair Family Physician Airways Group of Canada Past Chair of Special Interest Focused Practice, College of Family Physicians in Respiratory Medicine Chronic Pain Consultant Relationships with commercial interests: Have given one talk for Cannimed in March 2018

3 Disclosure of Commercial Support This program has received no financial support. This program has received no in-kind support. Potential for conflict(s) of interest: A) there are no organizations supporting this program B) I have given one talk for Cannimed in March 2018 C) EVERY DAY, I see patients admitted to hospital with the untoward effects of THC

4 Mitigating Potential Bias My bias is that smoking is BAD and is the major cause of preventable deaths I want to help patients manage their pain in a safe way

5 Objectives a) Understand the pros and cons of prescribing medical marijuana b) Understand the difference between CBD and THC c) Understand where to place medical marijuana in your pain management strategies

6 History

7 7 History Evidence from 3rd millenium BC Shakespeare might have used cannabis Queen Victoria- menstrual cramps Criminalized in 1906 (USA-DC)

8 8 CBD/THC Relationship Over 80 different cannabinoids in the cannabis plant influences effects Cannabinol, terpenes, terpenoids, flavenoids Main active ingredients are THC (tetrahydrocannabinol) and CBD (cannabidiol) Provide differe t pote cy a d therapeutic effects React differently with each person s biochemistry a d therefore have differe t pote tia for adverse or u desired effects Health Canada. Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids [Health Canada, 2013]. at

9 Natural Antagonism THC euphoria anxiety psychosis cognitive impairment tachycardia CBD no (or less) euphoria anti-anxiety anti-psychotic Neuroprotective Anti-inflammatory bradycardia Loss of antagonism may lead to increased side effects and poor tolerability.

10 10 Cannabidiol (CBD) Non-psychoactive cannabinoid? Second most common cannabinoid after THC Present in hemp Has unusual ability to antagonize CB 1 receptors at a low nm levels in presence of THC, despite having little binding affinity Can potentially modulate the effects on THC associated adverse events, such as memory impairment Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology. 2011;163(7): doi: /j x.

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13 CBD for psychosis?? Maybe CBD does not cause as much psychosis?? Treatment strategy???

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18 Effects of Drug Use on the Hippocampus Drugs of abuse are potent negative regulators of adult neurogenesis in the hippocampus Chronic administration of opiates, THC, ethanol or nicotine decreases hippocampal function, decreasing ability of adult brain to adapt to new information

19 Regional Brain Abnormalities Associated with Long-term heavy Cannabis Use Arch Gen Psychiatry 2008;65: long term (>10 years) and heavy (>5 joints daily) cannabis using men compared with 16 age matched non using controls by MRIs of brains Cannabis users had bilaterally reduced hippocampal and amygdala volumes p=.001 Increase in positive symptoms (psychotic) p<.001 Significantly worse performance on measures of verbal learning p<.001

20 Are Cannabinoids Addicting? Both heroin and cannabinoids increase dopamine levels in the nucleus accumbens This effect is blocked by naloxone When chronic THC use is stopped, the secretion of stress chemicals in the brain is similar to withdrawal from alcohol, cocaine or opioids Therefore THC behaves similar to other addicting drug Gianluigi, et al. Science 1997; 276: Rodriguez de Fonseca, et al. Science 1997; 276: Le Bec et al. Encephale 2009; 35(4):

21 % of Basal DA Output DA Concentration (% Baseline) Natural Rewards Elevate Dopamine Levels 200 FOOD NAc shell 200 SEX Empty Box Feeding Time (min) Source: Di Chiara et al. 100 Sample Number ScrScr BasFemale 1 Present Scr Mounts Intromissions Ejaculations Scr Female 2 Present Source: Fiorino and Phillips Copulation Frequency

22 % of Basal Release % of Basal Release Effects of Drugs on Dopamine Levels % of Basal Release Accumbens AMPHETAMINE DA DOPAC HVA hr Time After Amphetamine Accumbens MORPHINE Dose (mg/kg) hr Time After Morphine 250 NICOTINE THC/Marijuana Accumbens Caudate hr Time After Nicotine Source: Di Chiara and Imperato

23 Cannabis Dependency Percentage of people who have ever used drug Percentage of users who became dependent 76% Tobacco 32% 92% Alcohol 15% 46% Marijuana (Cannabinoids) 9% 13% 16% 2% Tranquilizers (and other prescription drugs) Cocaine Heroin 9% 17% 23%

24 Adverse Effects: Short-term anxiety, panic attacks distorted perception, hallucinations Cannabis use is associated with psychosis especially when started in the teenage years This increased risk may be as much as 2 4 fold increased heart rate and blood pressure decreased memory & learning difficulty thinking & problem solving decreased coordination visuomotor skills deficit *Actual impairment persists past perceived impairment* *Effects primarily associated with THC*

25 POT CHECK! What about Driving? Some evidence that marijuana use is associated with an increased risk of motor vehicle accidents It is illegal to drive in Ontario after smoking marijuana No data exists regarding what is a safe dose of medical marijuana to drive This also may vary depending upon the strain Effects of smoked marijuana last about 3 4 hours so prudent not to drive for at least 4 hours after smoking marijuana

26 Adverse Effects: Long-term immunosuppression inhalation: increased risk cancer of head, neck, lungs, respiratory tract increased risk testicular cancer occlusion brain arteries, increased stroke oculomotor control deficit hyperemesis syndrome associated with testosterone suppression and possible impotence. can increase prolactin in women leading to potential problems with ovulation and fertility

27 Adverse Effects: Long-term, cont. Neurological changes sustained decreased IQ associated with adolescents: change in neuroanatomy? altered memory, esp verbal decreased cerebral blood flow decreased neural efficiency increased DA neurotransmission, psychosis, anxiety disorder(s), schizophrenia younger age + extent of use + genetics mental illness

28 Cannabinoid Hyperemesis Syndrome chronic heavy users can develop severe nausea, emesis and abdominal pain which resolves once stopping marijuana

29 National Post September 1, 2017

30 Smoking is BAD! No other medication uses smoke as a delivery system Cannabis combustion produces hundreds of chemicals that are potentially toxic and carcinogenic Worsens lung function and increases cancer risk One joint = 8 cigarettes Smoking, vaporizing cause rapid rise and decline in serum THC levels Even 1-2 inhalations can cause cognitive impairment This is unacceptable for a long-term medication Rapid rise and fall sets up ideal addiction risk, as per Cigarette smokers

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32 32 Cannabis and death rates Study from compared 13 states with medical cannabis laws vs. no medical cannabis laws States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate (95% CI, -37.5% to - 9.5%; P =.003) compared with states without medical cannabis laws 1 In 2013 there were 0 deaths from marijuana 2 Have to consume 1/3 your bodyweight -to 15,000 pounds of cannabis all at once to reach the LD

33 Prescription Cannabinoids Pharmaceutical agents containing synthetic cannabinoids are available in Canada nabilone (Cesamet ) THC only (1mg $1.55) CBD/THC 1:1 (Sativex )(12.25/day) These are not medical cannabis, and are dispensed through pharmacies

34 Nabilone Synthetic THC Available in Canada for a number of years Useful for sleep, pain and nausea Should be trialed first before medical marijuana HOWEVER, many patients cannot tolerate because of sedation Starting dose is usually mg at night

35 Health Canada Dried marijuana is not an approved drug or medicine in Canada. The Government of Canada does not endorse the use of marijuana, but the courts have required reasonable access to a legal source of marijuana when authorized by a physician. Health Canada Government of Canada. Medical Use of Marijuana - Drugs and Health Products - Health Canada. Published June 13, Accessed December 13, 2014.

36 Legalization of Cannabis in Canada In April 2017, the government of Canada introduced the Cannabis Act to legalize and regulate recreational cannabis in Canada. The act is designed to decriminalize many aspects of cannabis use and distribution whilst reducing the legal burden of minor cannabis possession charges. The goal is to have this enacted into Canadian law by no later than July The act states that the current medical cannabis program in Canada will remain unchanged. At this point, it is impossible to determine what impact these changes will have on the medical cannabis patient. Positives could include lower cannabis cost as suppliers have a larger market for cannabis products and there can be easier access to cannabis through a wider number of retail settings. Issues include taxation of cannabis purchased through non-medical routes and a focus of LP s on the recreational market which could limit strains and products used by some medical users.

37 Assessment for Medical Marijuana Complete history and physical Addiction assessment including an ORT Collateral information Urine drug testing at time of assessment Patient agreement

38 Contraindicated if current alcohol/drug misuse Patients who report using medical marijuana, versus patients with similar pain conditions: Are more likely to use opioids problematically Are more likely to use cocaine Have worse psychosocial function Marijuana use worsens prognosis in substance users Aharonovich 2005, Mojarrad 2013

39 Contraindications/precautions to medical marijuana Youth < 25 Current/past hx psychosis Active substance use disorder Cardiovascular or respiratory disease Mood or anxiety disorder Pregnant/breast feeding

40 Pregnancy & Lactation *very lipophilic* Pregnancy: Unsafe Lower birth weight, shorter gestational period, abnormal startle response, tremulousness, smaller head size, premature labor, prolonged or arrested deliveries Lactation: Likely Unsafe Poor attention, concentration, and judgment, problem solving difficulties, ADHD

41 Cannabis Dependency Be aware that cannabis dependency does exist Remember the 4 C s Loss of Control Compulsive Use Cravings Use Despite Consequences.

42 Screening for risk?

43 Screening for risk?

44 44 The Process Pt consults authorized HCP HCP provides medical document Pt registers with LP and places order LP sends medical cannabis to pt Pt = patient HCP = healthcare provider LP = licensed producer

45 Medical document Patient and healthcare practitioner information, Duration of the prescription (maximum of 12 months), Daily quantity of cannabis in a number of grams, and May include any specific product recommendations, such as limiting THC concentration or restricting to cannabis oil only (NOTE: the licensed producer may not comply with these specifications).

46 46 Dosing High CBD - up to 20: 1THC High THC - up to 25: 0 CBD Hybrids anywhere in between

47 Cannabinoids: Inhalation vs Oral Characteristics Inhalation (vaporizing? YES) ng/ml Oral (oils or edibles) ng/ml THC Plasma Levels Absorption >95% 10 30% (up to 50%) Onset of Action within seconds min (up to 120 min) Duration of Action 2 3 (up to 4) hrs 5 8 (up to 12) hrs Adapted from Grotenhermen F. J Cannabis Ther 2003;3:3-51. Time during and after smoking (hours) Time after oral ingestion (hours) Note: For the purpose of image clarity, the y-axis of the Inhalation graph uses increments of 20 ng/ml and the y-axis of the Oral graph uses increments of 5 ng/ml. 48

48 49 Drug-Drug Interactions Pharmacokinetic There are no clinically significant drug interactions between cannabis and other medications Pharmacodynamic Noted interactions with drugs that cause similar side effects (e.g., opioids, benzodiazepines, anticholinergic medications, etc.) There is potential for additive dizziness, drowsiness and sedation 1.Abrams DI, et al. Clin Pharmacol Ther 2011;90: Geffrey AL, et al. Epilepsia 2015;56:

49 50 But!

50 And

51 What do I do? Comprehensive pain assessment of pain in the patient Pain effect, treatments, psychiatric history Phq9, GAD 7, BPI, UDS, Substance use risk Never a first line product for me

52 What do I do? Cannabis oils, high in CBD for pain Occasionally add in THC component for sleep at night only! Will use vaporizer rarely, in palliative care only, for more rapid response to pain as the long term harms are less relevant.. See q 1-3 months

53 Follow up

54 Conclusions Medicinal marijuana has a number of properties that can be useful in pain management. Not all strains are the same!! Like all treatments there is a risk benefit ratio Are we with MM now as to opioids 25 y ago?? Proper assessment including addiction screening are essential Apply the same goals and expectations with marijuana as you would with any other therapeutic agent Medical marijuana is a reasonable option for some but not all chronic pain patients (especially the higher CBD ratio strains) DO NO HARM!!

55 Who wants samples? 56 Discussion: