Medical Marijuana: Health Benefits and Considerations Elizabeth R. Aston, Ph.D. Department of Behavioral and Social Sciences Center for Alcohol & Addiction Studies Brown University AMSP 2019

What is Marijuana (MJ)? Leaves, flower, stems from cannabis sativa Includes many chemicals or “cannabinoids” Tetrahydrocannabinol (THC): responsible for high Cannabidiol (CBD): no high, medicinal properties Will use term “MJ”; use THC/CBD if specified in study AMSP 2019

MJ Background 22.2 million people in US in past month MJ legalization in US rapidly changing 1996: CA 1st to allow medical MJ 2019: 33 states & DC permit medical use 10 states & DC permit recreational use AMSP 2019

Pros and Cons of Medical MJ ↓ Pain ↑ Appetite ↓ Nausea ↓ Seizures ↑ Driving after MJ ↑ Poison control calls ↓ Perception of harm ↑ Problems for youth AMSP 2019

Lecture Covers Background & MJ components Disorders/symptoms with MJ proven benefits Disorders w/ limited data Clinical considerations Policy implications AMSP 2019

Case Example: Edna ♀, age 46, no history of MJ use Unusual symptoms Blurred vision, leg tingling, face numbness Trouble walking, muscle spasms Made primary care appt AMSP 2019

Lecture Covers Background & MJ components Disorders/symptoms with proven MJ benefits Disorders w/ limited data Clinical considerations Policy implications AMSP 2019

MJ Components Delta-9-tetrahydrocannibinol (∆9-THC) Major psychoactive component THC potency: ↑ in recent yrs 1995: 4%  2014: 12% Cannabidiol (CBD) Non-intoxicating; no craving May ↓ undesirable THC effects (e.g., intox) May have medical benefits (e.g., ↓ seizures) AMSP 2019

Possible Rx Cannabinoids* Terpenes –in many plants (e.g., oranges) Boosts MJ effects (e.g., ↓pain) Cannabigerol (CBG) – non-intoxicating ↓ inflammation & ↑ appetite in animals ↓ intraocular pressure Cannabichromene (CBC) – non-intoxicating CBC+THC ↓ inflammation in animals Blocks pain/inflammation (e.g., arthritis) * >100 components AMSP 2019

FDA Approved Cannabinoids (1) Synthetic oral THC Dronabinol (Marinol): Rx nausea/vomiting from chemo Rx appetite & weight loss in AIDS Nabilone (Cesamet): ↓ Brain signals controlling nausea/vomiting Rx severe nausea/vomiting from chemo AMSP 2019

FDA Approved Cannabinoids (2) Nabixmols (Sativex): CBD + THC Mouth spray, helps w/ muscle spasms Cannabidiol (Epidiolex): Plant-derived CBD No high or euphoric effects Approved by FDA to Rx pediatric epilepsy AMSP 2019

Randomized Controlled Trials (RCTs) Type of research design Patients get diff experimental Rx at random Gold standard for demonstrating drug effects AMSP 2018

Lecture Covers Background & MJ components Disorders/symptoms with proven MJ benefits Disorders w/ limited data Clinical considerations Policy implications AMSP 2019

Chronic Pain Condition for med MJ w/ most supporting data Affects ~30% of adults Opioids: ~259 million scripts US opioid overdose ↑ 4x over past 15 yrs ↑ availability worsens US opioid epidemic ~28 RCTs w/ ~2,500 chronic pain participants MJ ↓ pain compared to placebo *What do we have now and why would we be looking for an additional treatment? AMSP 2019

Severe Nausea MJ ↓ vomiting in animal studies Some patients prefer MJ over anti-nausea drugs ~28 trials show MJ effective Rx for nausea/vomiting: Placebo-controlled study w/ dronabinol Dronabinol =s other meds for nausea/vomiting Rx AMSP 2019

Severe Muscle Spasms Spinal injury Multiple sclerosis (MS): progressive ↓neuron Fx 15+ studies say MJ may ↓ spinal and MS symptoms 16% MS patients use MJ for Rx Placebo-controlled MS study Nabiximols given to ~200 subjects w/ MS MJ ↓ pain/spasms AMSP 2019

Check-In w/ Edna Attended primary care appt Suspected MS Testing included brain scans Started several Rx: Manage symptoms Slow disease progression AMSP 2019

Lecture Covers Background & MJ components Disorders/symptoms with proven MJ benefits Disorders w/ limited data Clinical considerations Policy implications AMSP 2019

Seizures Affects ~2.75 million in US Impairs cognitive development & life quality THC & CBD ↓ seizures in animals Human studies are lacking No high-quality RCTs Insufficient data that MJ ↓ seizures CBD OK for pediatric seizures AMSP 2019

CBD for Seizures Patients w/ oral CBD: 2 placebo-controlled RCTs 14 wk Rx period ~40% ↓ in seizure frequency Non-placebo study w/ 214 patients 12 wks oral CBD Seizures ↓ 54% AMSP 2019

Crohn’s Disease Colon inflamed w/ abdominal pain & bleeding MJ effective Rx for abdominal dx in animals Case report – MJ helped digestive disorders Retrospective MJ study for Crohn’s patients 30 patients already using MJ After MJ use general medical well-being ↑ AMSP 2019

Glaucoma ↑ Eye pressure & can → blindness Optic nerve damage from↑ pressure in eye MJ may ↓ eye pressure Single trial: small placebo-controlled MJ study See ~2 hrs intraocular pressure ↓ Pressure returned after 4 hours AMSP 2019

Cancer MJ prescribed to: ↑ appetite, ↓ cancer pain, ↓ chemo nausea Placebo-controlled study in advanced cancer Pain ± response to opiates Study w/ 3 doses of nabiximols Pain ↓ w/ nabiximols Nabiximols > placebo in low/med doses No human studies on MJ for Rx of cancer itself AMSP 2019

Neuropathic Pain Nerve damage pain (e.g., burning in feet) Affects ~2% of population Patients use MJ to ↓ pain, ↑ sleep & mood Placebo-controlled study 4 MJ doses in neuropathic pain patients High dose MJ (~9%) ↓ pain, ↑ sleep Lower doses & placebo did not help pain/sleep AMSP 2019

HIV/AIDS, Wasting Syndromes Severe weight/muscle ↓, no appetite Impacts patients w/ HIV/AIDS Evidence for MJ Rx still unclear MJ study not ↑ appetite or life quality Contradicts patient self-report Report MJ ↓wasting & ↑ appetite 1/3 with AIDS use MJ for symptom Rx AMSP 2019

Hepatitis C MJ doesn’t Rx Hep C or assoc liver disease May ↓ nausea assoc w/ Hep C meds May help w/ med adherence → better outcomes May ↓ med side effects One study found MJ worsens Hep C ↑ fibrosis (↑ connective tissue in liver) Alt study: MJ did not alter Hep C outcomes AMSP 2019

Dementia ↓ Thinking abilities (e.g., Alzheimer’s) No RCTS w/ MJ for agitation in Alzheimer’s Small 1-wk dronabinol study w/ dementia ↓ Agitation/aggression, ↑ appetite Small study w/ dronabinol for not eating Rx→ ↑ weight Small study: Dronabinol improves nighttime agitation AMSP 2019

Post-Traumatic Stress Disorder (PTSD) Severe stress symptoms following trauma No good RCTS w/ MJ for PTSD May ↑ sleep quality & ↓ nightmares Retrospective chart review study Nabilone for insomnia & nightmares Nabilone assoc w/ ↑ sleep, ↓ nightmares AMSP 2019

PTSD Retro chart review of patients w/ nightmares Rx w/ nabilone ~70% reported ↓ of nightmares & ↑ sleep 2 ongoing studies w/ MJ for PTSD Vets w/ PTSD get 1 of 3 MJ doses or placebo 1-yr symptom obs w/ users vs nonusers AMSP 2019

Anxiety No RCTs w/ MJ for anxiety One ongoing study w/ MJ for anxiety Subjects w/ anxiety High-CBD tincture (liquid drop under tongue) Outcomes: mood, life quality, sleep, health AMSP 2019

Check-in w/ Edna MS Rx side effects difficult to tolerate Tried many Rx w/ poor results Dr. suggested medical MJ for MS symptoms Edna obtained medical MJ card AMSP 2019

Lecture Covers Background & MJ components Disorders/symptoms where MJ has proven benefits Disorders w/ limited data Clinical considerations Policy implications AMSP 2019

Clinical Considerations Dose varies widely in active compound Research MJ doses: low: ~3% THC, high: ~12% THC Street doses: 10 – 90% THC Unclear which compounds result in desired effect Decreased perception of harm Potential malingering (faking bad) to get Rx AMSP 2019

Cannabis Use Disorder (CUD) DSM-5 CUD Criteria: mild, moderate, severe Tolerance Larger amounts used Much time spent using Attempts to cut down Neglecting major roles Important activities ↓ Interpersonal problems Phys/psych problems Hazardous use (e.g., driving) Craving Withdrawal Unclear how to assess for this among medical users – because they are going to fit some of the criteria because they use MJ daily as medication (e.g., craving, withdrawal, much time spent using, possibly tolerance) but that doesn’t necessarily mean they have CUD **Make reference here to how Edna and her Dr. need to pay attention to these symptoms as she begins using medical MJ (e.g., neglecting major roles, hazardous use) AMSP 2019

CUD Withdrawal Syndrome Mood effects: irritability, anger, depression Anxiety Sleep difficulty: insomnia ↓ appetite Restlessness Cognitive ↓ Phys symptoms: abdominal pain, tremors, sweating AMSP 2019

Lecture Covers Background & MJ components Disorders/symptoms where MJ has proven benefits Disorders w/ limited data Clinical considerations Policy implications AMSP 2019

Cons of MJ for Symptom Rx (1) Driving after MJ use has ↑ in med MJ states Poison control center calls ↑ ~50 in 2006 to ~250 in 2014 in med states Harm perception ↓ by 10% in teens in med MJ states Risk of ↑ MJ use & probs for young adult cardholders AMSP 2019

Cons of MJ for Symptom Rx (2) Doctors can’t prescribe or indicate dosage ~90% unprepared to rec MJ ~65% unable to answer MJ questions Few states require education for Drs. to rec MJ Dispensary – locale for MJ sale/purchase Med training usu. not req. for dispensary staff Make recs based on personal opinion CO dispensaries rec MJ for morning sickness **Risk of drug interactions due to limited research AMSP 2019

Pros of MJ for Symptom Rx Very effective for some illnesses States permitting medical MJ ↓ Opioid overdose ↓ Opioid prescriptions for those w/ Medicare Medical MJ associated w/ 64% ↓ in opioid use Patients report ↑ life quality & ↓ med side effects AMSP 2019

Edna’s Positive Outcome Began using MJ for MS symptom Rx Found low-dose edible that ↓ symptoms Began ↓ poorly tolerated meds w/ Dr supervision Successfully controlled MS symptoms w/ medical MJ Advocates for MJ benefits AMSP 2019

Take Away Points MJ promising for some conditions (e.g., chronic pain) MJ is not panacea for all illnesses Drs must attend to clinical considerations when rec MJ Several policy implications of rec MJ More MJ research is essential AMSP 2019