Update on Adolescent Cannabis Use Disorder

Educational Objectives

The goal of this program is to improve management of cannabis use disorder in adolescents. After hearing and assimilating this program, the clinician will be better able to:

1. Review recent data about cannabinoid therapeutics.
2. Discuss adverse effects of cannabis use during adolescence.
3. Describe psychosocial therapy approaches to reducing an adolescent’s cannabis use.

Summary

Introduction: views on marijuana polarized (eg, antimarijuana propaganda depicting it as evil drug that must be destroyed vs unrealistic messages that government suppressing information about ability of cannabis to cure cancer); important to embrace complexity of topic; cannabis can be potentially safe and benign, can contain potentially medicinal components, and can be potentially risky and harmful

Forms of cannabis use: use of cannabis dates back thousands of years; cannabis traditionally smoked, but edible products and more concentrated forms also available; cannabis smoked through blunts, joints, and vape pens and e-cigarettes (deliver vaporized tetrahydrocannabinol [THC]); wax is distilled, highly concentrated derivative of plant material with THC content 80% to 90%

Cannabis use and addiction: most users have occasional and benign experiences; some users more prone to addiction than others; compared to adults, adolescents at nearly 2-fold greater risk of becoming addicted or developing dependence

Potency of cannabis: has increased 4-fold over last 10 to 20 yr; average potency ≈14%; treatment admissions for cannabis use disorder correlated with potency; higher THC content associated with higher likelihood of cannabis use disorder; higher THC concentration and lower cannabidiol (CBD) concentration associated with higher propensity for addiction and adverse consequences

Endocannabinoid system: plays key modulatory role across many physiologic processes (eg, appetite, pain sensation, mood, memory, immune function, and neurodevelopment); involves cannabinoid receptor types 1 and 2 (CB1 and CB2) and endogenous cannabinoids (anandamide and 2-arachidonoylglycerol); THC binds to CB1 and CB2 receptors (psychoactive effects caused by CB1 binding)

Cannabis and cannabinoids: cannabis is complex plant with many active chemical constituents ∆-THC and CBD are 2 of them); >500 active chemicals and >100 active cannabinoids in smoked marijuana; many have dose-dependent effects; depending on state and regulations, typically no standardization of dose, potency, or chemical constituency; isolated and studied oral cannabinoids — dronabinol; nabilone; CBD; nabiximols (Sativex; standard-dose oral spray containing THC and CBD in 1:1 ratio)

Data about cannabinoid therapeutics: difficult to perform placebo-controlled blinded studies of smoked cannabis; most therapeutic studies have used orally dosed, isolated compounds; meta-analysis (Whiting et al, 2015) — looked at 79 randomized controlled trials (>6000 participants); found that most trials had high risk for bias; only 57% had appropriate blinding of participants, and only 24% had appropriate blinding of outcome assessors; many regulatory barriers to research are in place; only 2 studies used smoked or vaporized cannabis, and all others used oral compound; found moderate-quality evidence supporting treatment of chronic pain and spasticity, and increased risk for short-term adverse events; Food and Drug Administration (FDA) indications in place for dronabinol and nabilone; nabiximols under review for use in multiple sclerosis; recent studies show CBD associated with reducing frequency of seizures in Dravet syndrome; other study saw benefit of using CBD as adjunct for treatment of psychosis; smoked cannabis has no FDA indications; therapeutic evidence for cannabinoids limited to short-term use in adults with severe conditions; cannabis associated with potential for adverse events and addiction

Cannabis policy: federal — cannabis classified as Schedule I Controlled Substance (ie, deemed as having no medical use, lack of accepted safety for use under medical supervision, and high potential for abuse); states — at least 28 states and District of Columbia have legalized medical marijuana; at least 8 states have legalized recreational cannabis use; regulations vary between states

Considerations for adolescents: adolescents and families may assume that use of term “medical marijuana” means that marijuana beneficial; “natural” may imply that marijuana benign; important to remember that many medications or therapies (eg, warfarin, chemotherapy) can be helpful or toxic depending on user and dosage; annual Monitoring the Future survey — found that as marijuana increasingly legalized, adolescents’ perceptions of risk of cannabis use decreased, while rates of use increased; changes in policy have effects on adolescents’ perceptions, which then drive rates of use; adolescents may not use something they perceive as risky (eg, tobacco)

E-cigarettes: no FDA regulations about packaging; often packaged to appeal to adolescents (eg, various colors and flavors); among adults who are active tobacco smokers, switching to e-cigarettes associated with clear reduction in harm; however, exposing adolescents to nicotine through what is perceived as safer device may lead to perturbed brain development and progression to tobacco smoking

Brain development during adolescence: striatal circuitry develops more rapidly than prefrontal cortex; adolescents tend to value immediate rewards and engage in risky behaviors rather than considering long-term consequences; moreover, brain structures in transition more likely to be harmed by exogenous chemicals; cannabis initiation typically occurs during adolescence; 6% of daily or near-daily users often have significant adverse outcomes; younger users particularly prone to dependent symptoms and inability to reduce use; adolescents more likely than adults to progress quickly from occasional use to dependence

Adverse outcomes: heavier and earlier use of cannabis associated with adverse outcomes; heavy cannabis use in adolescence associated with adverse academic, occupational, and cognitive outcomes; with acute abstinence, cognition can return, but some longitudinal data indicate long-term cognitive decrement with heavy use; in clinical practice, adolescent cannabis use worsens course of psychotic, mood, and anxiety disorders; adult use tends to be more benign than adolescent use

Research: animal models — high-dose cannabinoids can be given to animals; data suggest that cannabis use during pregnancy and breastfeeding is problematic; this carries implications for neurodevelopment from in utero exposure; effects on growth have been demonstrated; ABCD Study — observational study that will follow 11,500 children 9 to 10 yr of age into adulthood under way; aims to track adolescent brain development through cognitive testing, mental health testing, academic performance testing, and neuroimaging; study large enough to track risk factors for, and adverse effects of, substance use

Psychosocial treatment of cannabis use in adolescents: motivational enhancement therapy — cornerstone of treatment; hardly any adolescents decide on their own that cannabis use is problem; rather, brought in by parent, school, or low enforcement; therefore, start by building rapport with adolescent; do not use confrontational tone; ask open-ended questions about cannabis use (eg, “What do you like about it?”) and eventually ask about any problems or dislikes about it; set goals toward behavior change; cognitive behavioral therapy — implement cognitive behavioral skills within motivational framework; work on, eg, refusal skills, anxiety management; family — family involvement often helpful; family can help deliver contingent reinforcement; contingency management — rewarding desired behavior; extrinsic reward (eg, voucher, gift card, or privilege) can drive behavior change (eg, abstinence to achieve negative urine test); outcomes — long-term abstinence generally poor; treatment results in reduced use, but adolescents tend to resume heavy use

Possible roles for medications: potential exists for targeting variety of behavioral mechanisms, including reducing effects of withdrawal, drug craving, and drug seeking; producing negative effects with drug use (aversion therapy); decreasing reward of substance use; reducing symptoms that drive self-medication

N-acetylcysteine (NAC): glutamate dysregulation in nucleus accumbens underlies drug-seeking behavior; NAC activates cysteine-glutamate exchanger in nucleus accumbens and upregulates glutamate transporter 1 (GLT-1) receptor, leading to decreased drug seeking in rodent models; randomized controlled trial — 116 adolescents received NAC (1200 mg twice daily) for 8 wk; study used contingent reinforcement (ie, participants received escalating cash rewards for attendance and for negative urine screening tests); NAC group had ≈2 times higher odds of having negative urine tests than placebo group (statistically significant); only 30% of participants in placebo group achieved negative urine testing; adult study — same design as adolescent study but more participants and slightly higher contingency rewords; adherence suboptimal; study found no difference between NAC group and placebo group (possibly attributable to, eg, poor adherence, potential effect being present in adolescents but not in adults, or heavier cannabis use by adults [adult baseline urine cannabinoid level more than double that seen in adolescents])

Conclusions: engage patients in discussion, avoid making polarizing statements and vilifying cannabis, and be nonconfrontational; evidence suggests greater harm than benefit with cannabis use in adolescence (especially with recreational use)

Readings

Camchong J et al: Adverse effects of cannabis on adolescent brain development: a longitudinal study. Cereb Cortex. 2017 Mar 1;27(3):1922-1930; De Gee EA et al: A randomized controlled trial of a brief motivational enhancement for non-treatment-seeking adolescent cannabis users. J Subst Abuse Treat. 2014 Sep;47(3):181-8; Fergusson DM et al: Psychosocial sequelae of cannabis use and implications for policy: findings from the Christchurch Health and Development Study. Soc Psychiatry Psychiatr Epidemiol. 2015 Sep;50(9):1317-26; Fernández-Artamendi S et al: Motivation for change and barriers to treatment among young cannabis users. Eur Addict Res. 2013;19(1):29-41; Gray KM et al: A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. Am J Psychiatry. 2012 Aug;169(8):805-12; Gray KM et al: A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults. Drug Alcohol Depend. 2017 Aug 1;177:249-257; O’Connell BK et al: Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy Behav. 2017 May;70(Pt B):341-348; Whiting PF et al: Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose. In his lecture, Dr. Gray presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Gray was recorded in Las Vegas, NV, at the 23rd Annual National Psychopharmacology Update, presented February 14-17, 2018, by the Nevada Psychiatric Association. For more information about this sponsor, visit www.nvpsychiatry.org/. The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

PG071301

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.