giving the green light to medicinal marijuananeuropathic pain from hiv-associated sensory neuropathy...

Giving the Green Light to Medicinal Marijuana

An Overview of NJ’s Program and Evidence

Shereef Elnahal, MD, MBACommissioner

Department of Health and Senior ServicesNJ Department of Health

Medical Cannabis Programs (MCPs)

• 33 states, the District of Columbia, Guam and Puerto Rico have MCPs or pending legislation1

• 13 states allow use of “low THC, high CBD” products for medical reasons in limited situations or as legal defense2

• 2.1 million certified in MCPs with mandatory registration; estimated total of 3.5 million MC users in the U.S.3

• Most common indications for MC:• Pain-related concerns (chronic pain, headaches)• Psychiatric disorders (anxiety, depression)• Insomnia

1. “State Medical Marijuana Laws.” National Conference of State Legislatures. 11 Feb 2019. http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx

2. “State Medical Marijuana Laws.” National Conference of State Legislatures. 11 Feb 2019. http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx

3. “Number of Legal Medical Marijuana Patients.” ProCon.org. 17 May 2018. https://medicalmarijuana.procon.org/view.resource.php?resourceID=005889

Courtesy Erin Zerbo, MDAssistant Professor, Department of Psychiatry, Rutgers NJ Medical School

http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx

http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx

https://medicalmarijuana.procon.org/view.resource.php?resourceID=005889


Significant Expansion in Murphy Administration

• 43,500 patients• 80 W OUD w

MAT • 905 physicians• 1,720 caregivers• 6 Alternative

Treatment Centers (ATC)


March 2018 Improvements:

• Expanded conditions• Reduced fees• Physician name

publication optional• Allow ATC satellites• Allow 2 caregivers per

patient


The Reason We Do This

• March 15 met an inspiring woman with ALS, going strong for over 7 years as a patient and advocate

• Medical Marijuana has helped Lindsay sleep, cope with chronic pain, and relieve her anxiety

• All of us are in this for people like her


Significant Improvements:

• Expanding Access:• 146 Applications rec’d 8/31 for up to 6 new ATCs

• Physician Friendly:• Doctors no longer required to be listed on public website (optional)• Number of physicians increased over 40 percent

• Provisional Caregiver Status (temp cards)• Expanding Product:

• Oil – oils that contain extracted THC and CBD that can be vaporized• Authorized pre-filled vape cartridges authorized mid-September 2018

• Mobile Access:• Patients, caregivers & physicians can access register, upload documents &

make payments on Smart phones & tablets (April 2018) • Revised Rules:

• Reviewing Comments; finalized soon


EO6: Proposed Regulatory Action:

• Streamline process for the addition of new conditions for treatment with medicinal marijuana

• Create separate endorsements in permitting process: dispensary, processor, cultivator

• Eliminate 10% THC limit

• Eliminate psychiatrist evaluation for minors


Pending Statutory Action

• Allow edible forms for all patients, not only minors • Allow patients access to more than one ATC • Allow marijuana as a first-line treatment for all

qualifying conditions • Eliminate 2 ounce per month limit for terminal

patients• Raise limit for all others over time• Remove non-profit requirement for original ATCs


Forms of Therapy

All Patients:• Oral – primarily lozenges that dissolve in mouth • Topical– oils, ointments, and other formulations

that are meant to be absorbed through skin • Flower – the “buds” that can be smoked, vaporized,

or baked

Adults:• Oil – oils that contain extracted THC and CBD that

can be vaporized• Pre-filled vape cartridges authorized

mid-September 2018

Minors:• Edibles – tablets, capsules, drops or syrups that

are ingested


Evidence: Chronic Pain

10

From: Cannabinergic pain medicine: a concise clinical primer and survey of randomized-controlled trial results. Aggarwal, Sunil K. The Clinical Journal of Pain. 29(2):162-171, FEB 2013

Objectives: This article attempts to cover pragmatic clinical considerations involved in the use of cannabinergic medicines in pain practice…..Methods: ….To survey the current evidence base for pain management with cannabinergic medicines, a targeted PubMed search was performed to survey the percentage of positive and negative published randomized-controlled trial (RCT) results with this class of pain medicines, using appropriate search limit parameters and the keyword search string “cannabinoid OR cannabis-based AND pain.”

Results: Of the 56 hits generated, 38 published RCTs met the survey criteria. Of these, 71% (27) concluded that cannabinoids had empirically demonstrable and statistically significant pain-relieving effects, whereas 29% (11) did not.


Design:• Patients were randomly assigned to smoke either cannabis (3.56%

tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted 3x daily for 5 days

Results:• Smoked cannabis reduced daily pain by 34%

Conclusion:• Smoked cannabis was well tolerated and effectively relieved chronic

neuropathic pain from HIV-associated sensory neuropathy• The findings are comparable to oral drugs used for chronic

neuropathic pain.

Evidence: HIV/AIDS

Cannabis in painful HIV-associated sensory neuropathy: A randomized placebo-controlled trial

Abrams, et al.,.Neurology. 2007 Feb 13;68(7):515-21.


Evidence: Rheumatoid Arthritis

Design:• In the first randomized controlled trial assessing efficacy of a cannabis-based

medicine (CBM) in treatment of pain due to rheumatoid arthritis (RA), a blend of whole plant extracts delivering approximately equal amounts of THC and CBD was compared with a placebo administered for 5 weeks

Results and Conclusion:• CBM produced statistically significant improvements in pain on movement, pain

at rest, quality of sleep and DAS28 (measure of disease activity) scores in patients with RA and was well tolerated

• Larger scale research is indicated

Preliminary Assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis Blake, et al. Rheumatology, Volume 45, Issue 1, 1 January 2006, Pages 50–52, https://doi.org/10.1093/rheumatology/kei183


Evidence: Inflammatory Bowel Disease

Design:• 13 patients with long-standing IBD who were prescribed cannabis

treatment were included. Two quality of life questionnaires and disease activity indexes were performed, and patient's body weight was measured before cannabis initiation and after 3 months' treatment

Results:• After 3 months' treatment, patients reported improvement in general

health, social functioning, ability to work, physical pain. Patients had a weight gain of 4.3 ± 2 kg during treatment

Conclusion:• Three months' treatment with inhaled cannabis improves quality of

life measurements, disease activity index, and causes weight gain and rise in BMI in long-standing IBD patients

Impact of cannabis treatment on the quality of life, weight and clinical disease activity in inflammatory bowel disease patients: a pilot prospective studyLahat el al., Digestion. 2012;85(1):1-8. doi: 10.1159/000332079. Epub 2011 Nov 17.


Evidence: Epilepsy

Design:• 213 patients qualifying for open-label Expanded Access study had to have a

treatment-resistant epileptic condition, such as Lennox-Gastaut and Dravet syndromes

• All patients were prescribed cannabidiol in a liquid daily dose that was gradually increased up to a potential maximum of 25mg/kg over 12 weeks

Results:• 137 patients completed the study• Number of seizures decreased by an average of 54%

Medical Marijuana Extract Curbs Seizure Frequency in Early Trial of Epilepsy PatientsDavinsky et al.., NYU Langone Medical Center 2015


Evidence: Multiple Sclerosis

Design:• 19‐week double‐blind, randomized, placebo‐controlled, parallel‐group study in

subjects with multiple sclerosis spasticity not fully relieved with current therapy

Subjects were treated with nabiximols as add‐on therapy

Results:• 272 of 572 subjects achieved a ≥20% improvement after 4 weeks

Conclusion:• Study design provides a method of determining the efficacy/safety of

nabiximols that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it

The difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment

A randomized, double‐blind, placebo‐controlled, parallel‐group, enriched‐design study of nabiximols* (Sativex®), as add‐on therapy, in subjects with refractory spasticity caused by multiple sclerosis

Novotna, et al. European Journal of Neurology 2011


Medical Marijuana w MAT to Treat Opioid Use Disorder

• OUD is a public health crisis requiring all resources to combat its harmful effects (EO# 219 2017)

• MM can be prescribed in NJ w MAT regimen for treatment of OUD (March 2018)

• Potential to ease:• Opioid withdrawal symptoms • Reduce opioid consumption• Ameliorate opioid cravings• Prevent opioid relapse• Improve OUD Treatment Retention• Reduce OD deaths (3,163 deaths in 2018)


Evidence: Opioids and Opioid Abuse

Design:• Population-based, cross-sectional, longitudinal analysis of Medicaid prescription

claims data for 2011 to 2016

Results:• State implementation of medical marijuana laws was associated with a 5.88% lower

rate of opioid prescribing (95% CI-11.55% to approximately -0.21%)• The implementation of adult-use marijuana laws in states with existing medical

marijuana laws was associated with a 6.38% lower rate of opioid prescribing (95% CI-12.20% to approximately -0.56%)

Conclusion:• The potential of marijuana liberalization to reduce the use and

consequences of prescription opioids among Medicaid enrollees deserves consideration during the policy discussions about marijuana reform and the opioid epidemic.

Association of Medical and Adult-Use Marijuana Laws With Opioid Prescribing for Medicaid Enrollees

Wen et al., JAMA Intern Med. 2018;178(5):673-679. doi:10.1001/jamainternmed.2018.1007


Evidence: Opioids and Opioid Abuse

Design:• Longitudinal analysis of the daily doses of opioids filled in Medicare Part D for all opioids

as a group and for categories of opioids by state and state-level Medical Cannabis Law (MCL) from 2010 through 2015.

Results:• Analysis results found that patients filled fewer daily doses of any opioid in states with an

MCL States with active dispensaries saw 3.742 million fewer daily doses filled

Conclusion:• Medical cannabis laws are associated with significant reductions in opioid prescribing in

the Medicare Part D population. This finding was particularly strong in states that permit dispensaries, and for reductions in hydrocodone and morphine prescriptions.

Association Between US State Medical Cannabis Laws and Opioid Prescribing in the Medicare Part D Population

Bradford et al., JAMA Intern Med. 2018;178(5):667-672. doi:10.1001/jamainternmed.2018.0266


From: The use of cannabis in response to the opioid crisis: A review of the literatureBeare Vyas, et al. Nursing Outlook. 2017

Evidence: Use of Cannabis in Response to Opioid Crisis

“The use of [medical cannabis] as an alternative to [prescription opioids] for pain management warrants additional empirical attention as a potential harm reduction strategy…”

• 10 studies included in final review• Consistent evidence of reduced opioid use by patients also

using Medical cannabis • Consistent evidence of reduced opioid prescribing/use with

increased availability of cannabis.


CBD for Opioid Use Disorder

• Hurd: “Strong scientific basis” for using CBD for OUDs• Very safe and not rewarding—like opioids• “Indisputable” evidence that they modulate anxiety

• ECS involved in stress responsivity & negative emotional states • CBD inhibits FAAH and ↑ anandamide weak agonism at CB1

receptor leads to enhanced physiologic tone and reduced anxiety (strong agonism can cause anxiety/psychosis)

• CBD reduces amygdala activity• CBD reduces rewarding properties of opioids and

withdrawal symptoms; reduces heroin-seeking behavior (a long-lasting effect)

• CBD normalizes heroin-induced impairment of CB1R and glutamate receptors in the striatum

Hurd YL. Cannabidiol: Swinging the Marijuana Pendulum from ‘Weed” to Medication. Trends Neurosci 2017.


Short term side effects

Marijuana Benzodiazepines Opioids SteroidsSedation Sedation Sedation Fluid retention

Impaired short-term memory Dizziness Dizziness High blood pressure

Impaired motor coordination Weakness Nausea

Problems with mood, memory, behavior

Altered judgement Unsteadiness Vomiting Weight gain

Paranoia Loss of orientation Constipation Insomnia

ConfusionRespiratory depression Blurred vision


Effects of long term use

Marijuana Benzodiazepines Opioids Steroids

Associated with greater risk of developing psychoses Cognitive impairment Constipation CataractsIncreased risk of social anxiety disorder Adverse effects on sleep

Sleep-disordered breathing High blood sugar

Potential lasting cognitive deficits

Increased risk of fall and fracture

Increased risk of overdose (2 in 1000 risk of death)

Increased risk of infections

Increased risk of bronchitis (smoking only)

Increased risk of depression, anxiety, other mental health conditions Depression Thinning bones

Risk of severe withdrawal after only 1 month of regular use

Increased risk of fall and fracture

Suppressed adrenal gland hormone production

87% increase in all cause mortality

Thin skin, bruising, slower wound healing


Addiction, Withdrawal, OD

MarijuanaPrescription Benzodiazepines Prescription Opioids

Use disorder prevalence 9%

As many as 23% of long term users 8-12% develop addiction

Severity of withdrawal Minor Major Major

Worst Symptoms

Dysphoria, Disturbed Sleep, Decreased Appetite

Severe Depression, Catatonia, Convulsions, Death

Abdominal Cramps, Pain, Anxiety, High Blood Pressure, Severe Cravings, Depression

Overdose Deaths (2015) 0 8,791 22,598


Out of everyone who has tried once, percent who develop a use disorder:

Nicotine: 32%Heroin: 23%Crack, IV cocaine: 23%Intranasal cocaine: 17%Alcohol: 15%Cannabis: 9%Sedative-hypnotics: 9%Inhalants: 3.7%

Addictive Spectrum



• No conclusive health-threatening dangers yet found

• Correlational studies:• Brain changes in adolescents• Long-term memory deficits / lower IQ• Addiction to more dangerous drugs• Increased incidence of psychosis

• NIDA’s Alan Leshner: “congressional mandate forbids funding research to uncover benefits”• $66 million per year to determine harms of cannabis


After 45 years & 1,800 studies…


U.S. Cannabis Research

• >20,000 experimental studies but few definitive clinical trials

• Lots of red tape for researchers in the U.S.• NIDA, DEA and FDA

control access to cannabis since 1968

Federal Marijuana Farm, University of Mississippi



Promising, but not for everyone

Recommendation of medicinal cannabis use must be weighed extra-carefully for the following populations:

• Children• Pregnant women

For children: evidence suggests that adolescent cannabis use correlates with negative effects on brain development, and can lead to increased risk of developing cannabis use disorder later in life.

For pregnant women: evidence suggests that cannabis use leads to lower birth weight. Longer term effects on children need to be studied, but limited evidence points to potential negative effects on attention span and learning after birth.


Requirements & Eligibility

Physician requirements:

• Active NJ medical license, in good standing, issued by the Board of Medical Examiners;

• Active Controlled Dangerous Substances (CDS) registration, issued by the NJ Division of Consumer Affairs, which is not subject to limitation; and

• Practice within the State of New Jersey.


Requirements and Eligibility

Qualifying Conditions

Debilitating:

Amyotrophic lateral sclerosis Multiple sclerosis Terminal cancer Muscular dystrophy Inflammatory bowel disease (IBD), including Crohn’s disease Terminal illness, if the physician has determined a prognosis of less than 12 months of life.

Resistance, or intolerance, to conventional therapy: Seizure disorder, including epilepsy Intractable skeletal muscular spasticity Glaucoma Post-Traumatic Stress Disorder (PTSD)

Severe or chronic pain, severe nausea or vomiting, cachexia or wasting syndrome resultingfrom the condition or treatment of: Positive status for human immunodeficiency virus (HIV) Acquired immune deficiency syndrome (AIDS) Cancer


Breakdown of New Patients


Requirements and Eligibility: Chronic Pain

Qualifying Conditions

Chronic pain related to musculoskeletal disorders – Accepted petitions

Chronic painChronic non-cancer painChronic pain as a result of daily sciatic nerve pain Sporadic hemiplegic migraineComplex regional pain syndrome Neural foraminal stenosis Cauda Equina Syndrome Arnold-Chiari Malformation Neuropathic PainRheumatoid Arthritis; Arthritis; Psoriatic Arthritis Systemic LupusChronic late stage Lyme’s disease with pain and depressionOpioid use disorder Fibromyalgia/Osteoarthritis


Testing

DOH Public Health Environmental Lab Department of Agriculture

Cannabinoid Profile Metals Pesticides

Mold Other contaminants

126 distinct strains Lab tested


Dosing for New Patients

• Emphasize vaporizing or oral administration over smoking

• For oral administration, strongly advise limiting THC initially to under 5mg per dose (under 2.5 mg if they want to limit impairment). Standard dose of THC is 5-10 mg

• Oral administration usually can take 2+ hours to take effect with these effects lasting longer versus vaporization and smoking

• Advise new patients to wait at least 2 hours before taking an additional dose, or preferably wait to adjust next dose. Recommend they increase dose incrementally (adding no more than 5mg THC)

• For vaporization and smoking, recommend they start with no more than 2-3 inhalations, 1 at a time, with a few minutes in between

• CBD has not been shown to have psychoactive effects on its own, so for patients that want to limit impairment, recommend a high CBD (>5%)/low THC strain(<5%)


Q+A

• Customer Service Number: (609) 292-0424

• Customer Service Email: [email protected]

•www.state.nj.us/health/medicalmarijuana/contact

Follow us on Twitter: @ShereefElnahal

@NJDeptofHealth

mailto:[email protected]

http://www.state.nj.us/health/medicalmarijuana/contact

giving the green light to medicinal marijuananeuropathic pain from hiv-associated sensory neuropathy...

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