Medical Cannabis

Joshua Dowd, MD

Hospice and Palliative Medicine Physician

Delving into the Weeds

Disclosures

• None

Agenda

• History of how cannabis came to be illegal

• Current laws, regulations, and research challenges

• Cannabis and cannabinoids

• Use of cannabis and its effects

• Data for therapeutic effects and adverse effects

• FDA-approved medications

• Cannabis and renal disease

• Cannabis and the opioid epidemic

• Bottom line, practical approach to medical cannabis

What Do We Mean by Cannabis?

• Cannabis:

– A psychoactive drug from

the Cannabis plant used for

medical or recreational

purposes

• Don’t you mean marijuana?

Wang 2019, Wikipedia 2019

History and Laws

Early Days

NASEM 2017, Wikipedia 2019

So What Went Wrong?

• 1906 – Pure Food and Drug Act

passed

• 1910s – Mexican Revolution

• 1930 – Federal Bureau of

Narcotics formed

Wikipedia 2019, Wilcox 2014

Harry Anslinger

• “Marijuana is the most violence-causing drug in the history of mankind…and most

[marijuana smokers] are Negroes, Hispanics, Filipinos, and entertainers. Their satanic

music, jazz, and swing, result from marijuana usage. This marijuana causes white

women to seek sexual relations with Negroes, entertainers, and any others.”

• “Reefer makes darkies think they’re as good as white men…the primary reason to

outlaw marijuana is its effect on the degenerate races.”

Wikipedia 2019, Wilcox 2014

Reefer Madness

YouTube 2011

More Laws

• 1937 – Marihuana Tax Act

• 1970 – Controlled Substances Act

Wikipedia 2019, Wilcox 2014

The Times They Are A Changin’

• 1996 – CA Proposition 215 approved

• 2012 – CO and WA legalized recreational use

NC:

• 1977 – Decriminalized

• 2015 – CBD legalized for intractable epilepsy

• 2017 – Hemp farming legalized

Wikipedia 2019

Public Opinion and Use

Wang 2019, Wikipedia 2019

Research Difficulties

Wikipedia 2019

Cannabis

Cannabis

Rahn 2018, Wikipedia 2019

Cannabinoids

NASEM 2017, Park 2017, Rahn 2018, Wang 2019, Wikipedia 2019

THC and CBD

Christensen 2018

NASEM 2017

Rahn 2018

Wikipedia 2019

Using Cannabis

• Routes

• Products

Aggarwal 2015, Davison 2011, Ho 2019, NASEM 2017, Rahn 2018,

VandeKieft 2018, Wang 2019, Wikipedia 2019, Williams

Inhalation Oral Topical

Onset: <15 min 30 min – 3 h 15 – 45 min

Duration: 1 – 3.5 h 5 – 8 h or longer 2 h

Flowers Resin Oil

THC (%): 5-20% 40-80% 75+%

What Happens When We Use? • With Effective Doses:

– Decreased short term memory

– Impaired perception and motor skills

– Ataxia

– Slurred speech

– Enhanced sensitivity to stimulation

– Altered perception of time

– Increased appetite

– Euphoria

– Red eyes

– Decreased intraocular pressure

– Dry mouth

– Tachycardia

– Orthostatic hypotension

– Tachypnea

– Muscle relaxation

NASEM 2017, Wang 2019, Wikipedia 2019

• With Very High Doses: – Psychosis

– Hallucinations

– Paranoia

– Panic attacks

– Asthma exacerbations

– Pneumomediastinum

– Pneumothorax

– Acute coronary syndrome

– Cannabis hyperemesis syndrome

• What about overdose,

withdrawal, or dependence?

Let’s Talk about Data

Aggarwal 2015, NASEM 2017

Therapeutic Effects

• Conclusive/Substantial Evidence for Effectiveness:

– Chronic pain in adults

– Chemotherapy-induced nausea/vomiting

– Patient-reported multiple sclerosis-related spasticity

• Moderate Evidence for Effectiveness:

– Sleep disturbance related to OSA, fibromyalgia, chronic

pain, MS

NASEM 2017

Therapeutic Effects

• Limited Evidence for Effectiveness:

– HIV/AIDS-related anorexia and wasting

– Clinician-reported MS-related spasticity

– Tourette syndrome

– Anxiety

– PTSD

– Better outcomes after TBI/ICH

• Limited Evidence for Ineffectiveness:

– Dementia

– Glaucoma

– Depression in patients with chronic pain or MS

NASEM 2017

Therapeutic Effects

• No/Insufficient Evidence for Effectiveness:

– Cancer

– Cancer-related anorexia

– Irritable bowel syndrome

– Epilepsy

– Spasticity in patients with spinal cord injury

– ALS

– Huntington’s disease

– Parkinson’s disease

– Dystonia

– Abstinence from other addictive substances

– Schizophrenia

NASEM 2017

Effects for Movement Disorder

YouTube 2017

Adverse Effects

• Substantial Evidence:

– Worse respiratory symptoms with bronchitis (smoking)

– Increased risk of motor vehicle crashes

– Lower birthweight of infants

– Development of schizophrenia

• Moderate Evidence:

– No increased risk of lung or head/neck cancer (smoking)

– Increased risk of overdose injuries in children in legal states

– Increased risk of depression, mania in bipolar disorder,

social anxiety disorder, suicidal ideation and completion

– Development of substance use disorder of other substances

NASEM 2017

Therapeutic Effects

• Limited Evidence:

– Increased incidence of some testicular cancers (smoking)

– Triggering acute MI (smoking)

– Increased risk of stroke

– Decreased risk of diabetes and metabolic syndrome

– Increased risk of developing COPD

– Pregnancy complications for mother

– NICU admissions for infants

– Impaired academic, employment, or social achievement

– Increase in positive symptoms for those with psychosis

– Increased risk of developing bipolar disorder or anxiety

– Increased severity of PTSD

– Initiation of tobacco abuse NASEM 2017

Therapeutic Effects

• No/Insufficient Evidence:

– Incidence of other cancers

– Developing asthma

– COPD hospitalizations

– Adverse immune responses

– All-cause mortality

– Occupational accidents

– Later infant outcomes (i.e.. Not right after birth)

– Developing PTSD

NASEM 2017

FDA-Approved Medications

• Dronabinol (Marinol)

• Nabilone (Cesamet)

• Epidiolex

Davison 2011, NASEM 2017

Dronabinol (Marinol)

• Synthetic delta-9-THC

• Approved for chemo-induced nausea/vomiting and

AIDS-related anorexia

• Formulation: Oral capsule and solution

• No adjustment for renal or hepatic dysfunction

• No lab monitoring

• Onset: 30-60 minutes

• Duration: 4-6 hours

• Half life: 19-56 hours

• Urine THC positivity: Yes

Davison 2011, NASEM 2017

Nabilone (Cesamet)

• Synthetic analog of delta-9-THC

• Approved for chemo-induced nausea/vomiting

• Formulation: Oral capsule

• No adjustment for renal or hepatic dysfunction

• No lab monitoring

• Onset: 60-90 minutes

• Duration: 8-12 hours

• Half life: 2 hours

• Urine THC positivity: No

Davison 2011, NASEM 2017

Epidiolex

• Concentrated (98%) CBD oil

• Approved for seizures associated with Lennox-Gastaut

syndrome or Dravet syndrome in patients >2 yo

• Formulation: Oral solution

• No adjustment for renal dysfunction

• Adjustment needed for hepatic dysfunction

• Monitor LFTs due to risk of hepatotoxicity

• Onset: Within 4 weeks

• Half life: 56-61 hours

• Urine THC positivity: No

Davison 2011, NASEM 2017

Nabiximols (Sativex)

• THC:CBD extract from 2 Cannabis varieties

• Not approved in US

• Approved in other countries for MS-related spasticity

or neuropathic pain

• Formulation: Buccal/oral spray

• No adjustment for renal or hepatic dysfunction

• No lab monitoring

• Onset: 30-150 minutes

• Duration: 6-8 hours

• Half life: 1.5 hours

• Urine THC positivity: Yes

Davison 2011, NASEM 2017

Cannabis and Renal Disease

• THC partially excreted in urine

– Effects may last longer

• CBD mostly excreted in feces

– Effects may not be effected

• Cannabinoids highly protein bound

and lipid soluble

– May not be dialyzed well

• Renal system has CB1 and CB2

– No data on effects

Aggarwal 2015, Davison 2011, Ho 2019, NASEM 2017

Symptom Relief for CKD?

Davison 2011, Ho 2019

Renal-Specific Data

• Cohort of 21 patients undergoing HD with uremic pruritus

• Cream with lipids and cannabinoids bid for 3 weeks

• Pruritus completely eliminated in 38%

• Xerosis completely reduced in 81%

• Xerosis intensity did not correlate with pruritus severity

– Assumed that xerosis was not the main contributor to pruritus

• No adverse effects

Szepietowski 2005

Renal-Specific Data

• Cohort study of 7 patients s/p kidney transplant with chronic pain

who asked to receive CBD to treat their pain

• CBD 50mg bid increased up to 150mg bid for 3 weeks

• 2 had total pain improvement, 4 had partial, 1 had no change

• Adverse effects: nausea, dry mouth, dizziness, drowsiness

• CBD dose reduction was needed in 2 patients

• Tacrolimus levels may have been effected

Cuñetti 2018

Cannabis and the Opioid Epidemic

Cannabis and the Opioid Epidemic

• Fewer deaths does not mean cause and effect

• Laws don’t address non-prescription opioid abuse

• Only case reports about using cannabis to taper

• No evidence for use to treat opioid use disorder

• Strong evidence-based treatments are underutilized

Voelker 2018

Cannabis and the Opioid Epidemic

• Highlighted largest cohort study with cannabis as a substitute

– 1500 patients over 4 years

– Associated with more pain, less self-efficacy, and same opioid use

• Using cannabis to treat opioid use disorder is using the failed

tactic of replacing addictive substances with others

• Cannabis products are highly variable

– Of 84 studied CBD extracts, 69% were mislabeled

• Risks have evidence, substitution does not

Humphreys 2019

What’s the Bottom Line?

Overall Approach

• Practical approach from American Pain Society:

– Know federal and state laws governing medical cannabis

– Be clear with patients about goals for therapeutic cannabis

– Screen for risk of misuse, addiction, and diversion

– Counsel patients about routes, benefits, risks

– Advise patients on strains, medications, extracts, limitations

– Monitor patients as you would for treatment with opioids

– Assess progress toward achieving goals, side effects

– Continue or discontinue based on observed outcomes

Savage 2016, VandeKieft 2018

Approach for Chronic Pain

• Think about cannabis before opioids

• Should be part of an integrated, patient-centered program

emphasizing non-pharmacologic options

• Oral capsules for long action, tinctures/vaping for short action

• Start low (with CBD) and go slow:

– CBD 5-10mg PO bid

– Increase weekly over 1-2 months until relief

– If no relief, add THC 1-2mg and slowly increase

• Delayed THC hopefully avoids dysregulation of

endocannabinoid system (extrapolated from opioid use)

Boehnke 2019

My Takeaways

• The history of how cannabis became illegal is concerning

• Research needs to be easier than it is

• Start with low THC, go slow

• Vaporize for short-term, oral for long-term, don’t smoke

• Not a magic bullet, but another tool in the toolbox for

challenging symptoms

• Use definitely has real risks

• Sounds safe in patients with renal dysfunction

• Definitely not the solution to the opioid epidemic

References

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Wisconsin. Available at: https://www.mypcnow.org/blank-vg8y7. Updated Sep 2015. Accessed May 12, 2019.

2. Boehnke KF, Clauw DJ. Brief Commentary: Cannabinoid Dosing for Chronic Pain Management. Ann Intern Med. 2019

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3. Briscoe J, Kamal AH, Casarett DJ. Top Ten Tips Palliative Care Clinicians Should Know About Medical Cannabis. J Palliat

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4. Christensen A, Pruskowski J. Fast Facts and Concepts #370: The Role of Cannabidiol (or CBD) in Palliative Care. Palliative

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5. Cuñetti L, Manzo L, Peyraube R, Arnaiz J, Curi L, Orihuela S. Chronic Pain Treatment With Cannabidiol in Kidney

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https://www.youtube.com/watch?v=pC17CaLU74I. Published Feb 24, 2017. Accessed May 12, 2019.

10. National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current

State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press; 2017.

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Questions and Thank You!