Cognitive Ramifications of Adolescent Cannabis Use

© Alcohol Medical Scholars Program

Randi M. Schuster, Ph.D.

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School

I. Introduction

            A. Case Presentation: JM

                        1. Demographics (SLIDE 3)

a. 18yo

b. Male

c. Hispanic

                        2. Academic (SLIDE 3)

a. 4th year student at prestigious Boston-area university

b. A good student in high school

c. “OK” grades in college

d. ↑ difficult to absorb material in lectures and when studying

                        3. Psychiatric (SLIDE 3)

                                    a. No hx of treatment

                                    b. But met criteria for major depressive episode at our first meeting

                        4. Substance use at start of treatment (SLIDE 4)

                                    a. Never use of drugs other than alcohol and cannabis

                                    b. Drank max 1 day/week, 3 drinks/occasion

                                    c. Cannabis (MJ) use

                                                1’. Tried at age 13

                                                2’. Started using regularly (>1x/wk) age 15  

                                                3’. Currently smokes 2x/day; ~1-2grams/day

                                                4’. MJ use dependence (DSM-IV)

                                                5’. THC levels >500ng/mL

                                                6’. “I don’t like thinking. Smoking makes my brain go quiet.”

                        5. Changes after 30 day treatment (SLIDE 5)

                                    a. Substance use (SLIDE 5)

                                                1’. No change in alcohol use

                                                2’. 30 days of continuous MJ abstinence

                                                3’. THC levels undetectable

                                    b. Psychiatric (SLIDE 6)

                                                1’. Improvement in self-reported mood

2’. “Doc! I had such a #$&%#$ day. I wanted to burn one so bad. You would be proud--I mowed my backyard instead! It kind of made me feel better.”

            c. Cognitive (SLIDE 7)

                        1’. ↑ attention

                        2’. ↑ executive functions

B. This lecture reviews: (SLIDE 8)

                       1. Epidemiology of adolescent MJ use and consequences

                       2. Normative brain maturation in adolescence and relevance to MJ use

                       3. Cognitive consequences of adolescent MJ use

II. Epidemiology and Course of Adolescent MJ Use  

A.    MJ basics

1.      What is MJ? (SLIDE 10)

a.       Cannabis sativa or Cannabis indica

b.      Dry, shredded leaves, flowers, stems, and seeds

c.       >400 chemical compounds

2.      How is MJ used? (SLIDE 11)

a.       Smoked

b.      Vaporized

c.       Ingested

B. Shifting cultural context surrounding MJ use (SLIDES 12 AND 13)

                        1. 4 states legalized MJ (Oregon, Washington, Alaska, Colorado) + D.C.

                        2. More states expected similar initiatives in 2016

3. Potential to ↓ barriers to access and ↑use further

C. Rates of MJ use among youth (SLIDE 15)

1.  Most likely drug tried by 8th grade, after alcohol and cigarettes

2. 22M (8.4%) people aged 12+ past month MJ users [1]

            D. MJ use ↑ across adolescence (SLIDE 16)

1. Ever tried

                                    a. ~17% 8th graders

                                    b. >33% 10th graders

                                    c. ~50%12th graders

                        2. Past year use

                                    a. 12% 8th graders

                                    b. 27% 10th graders

                                    c. 35% 12th graders                            

3. Current use (past month)

                                    a. 7% 8th graders

                                    b. 17% 10th graders

                                    c. 21% 12th graders

                                    d. Now surpasses rates of daily alcohol and tobacco use

E. Availability, potency and perception of MJ use rapidly changing (SLIDE 17)

1.  ↑ Potencies

a. In 1960s-70s potency ~1-2% of THC

b. Today, up to 20-25% THC

2. ↓ harm perception in high schoolers since mid-2000s [2] (SLIDE 18)

                        a. 36% think MJ harmless

                        b. ~43% favor legalization (80s: 15%; 90s-00s: 30%) 

c. Perception of harm is lowest in 40 years

d. ↓ harm perception often precedes ↑ prevalence [3, 4]

F. Consequences of MJ use in adolescence

1. MJ is used despite functional consequences (SLIDE 20)

a. 17% of teen-onset users have MJ use disorder (9% in later-onset) [5, 6]

b. ↑ MJ use disorder dxs than other illicit drugs

                        1’. ~2.5M adolescents (12-25yrs) with a cannabis use disorder

                        2’. ~11x> cocaine

                        3’. ~13x> heroin

c. More age 12-25 in tx than any other illicit drug

1’. Overall 355k adolescents in 2014

2’. ~4x > for cocaine

3’. ~2x > heroin

                                    d. ↓ age of onset, ↑ MJ dependence (SLIDE 21)

2. MJ has withdrawal syndrome after chronic use (SLIDE 22)

a. Irritability

b. Sleeping difficulties

c. Craving

d. Anxiety

e. Appetite change

f. Physical symptoms (e.g., fever, headache, shakiness, muscle pain)

            3. Academics (SLIDE 23)

a. High school dropout ~2x > non-users [7]

b. 4x ↑ use if non-college-bound [8]              

4. Other substance use (SLIDE 24)

a. Heavy MJ users ↑ use other illicit drugs later [9]

            1’. Weekly use → 2-3x more likely to use illicit drug use later

2.’ Daily use → ↓ cessation rates of later illicit drug use

                        5. Psychiatric (SLIDE 24)

a. Early users have ↑ later severe psychoses (e.g., hear voices) [10, 11]

b. ↑ risk for later anxiety or depressive disorder [12-14]

c. ↑severity and duration of some major psychiatric symptoms [15]

III. MJ & Adolescent Brain Development

A. Cannabis mimics natural endogenous cannabinoids (e.g., anandamide) (SLIDE 25)

1. Δ9-tetrahydrocannabinol (THC), cannabis’ 1° psychoactive constituent

2. Acts on pre-synaptic cannabinoid receptors (CB1)

3. THC and anandamide are inhibitory, but THC binds longer and stronger

B. Dynamic alterations in endocannabinoid function in the adolescent brain

1. THC binding sites; plentiful in: (SLIDE 26)

a. Front of the brain: prefrontal cortex

b. Back of the brain: cerebellum (coordination) and visual center

c. Middle of the brain: reward system, hippocampus (memory), hypothalamus (appetite, body temperature, emotions, digestion, etc.), and thalamus (receives and relays sensory information such as pain)

2. CB1 receptors ↑↑↑ from infancy to age 30 (SLIDE 27)

3. Most and latest change in areas of [16]:

a. Reward and Motivation (e.g., Striatum, orbitofrontal cortex)

c. Cognition (e.g., Prefrontal cortex, insula, hippocampus)  

C. Brain development damage from MJ, including abnormalities in: (SLIDE 28)

1. Size/shape/function of brain [17]

a. Particularly structures important for:

1’. Reward and Motivation [18-20]

2’. Cognition [19-22] 

2.      And how these brain structures communicate with each other [23-25]

3.      Earlier use → ↑ brain abnormalities  

IV. Exaggerated Cognitive Ramifications of MJ Use During Adolescence

            A. Acute cognitive effects (SLIDE 30)

                        1. Paranoia

                        2. Attention and psychomotor processing speed

                        3. Memory

                        4. Motivation

            B. Preliminary evidence for longer-lasting cognitive effects

                        1. Likely linger beyond acute intoxication (SLIDE 31)

                                    a. Withdrawal syndrome lasts ~2wks

b. Cannabinoids linger in CNS for ~4 weeks [26]

2. Memory (SLIDE 32)

                                    a. Learning new information

                                    b. Remembering new information later

                        3. Attention and concentration (SLIDE 32)

                                    a. Response speed

                                    b. Response speed variability

                        4. Executive functioning (SLIDE 32)

a. Working memory

                                    b. Verbal fluency

                                    c. Decision-making and risk-taking

                                    d. Inhibitory control

                        5. Earlier use is worse (SLIDE 33)

                                    a. ↓ age of initiation worse cognition

                                    b. ↓ age of initiation ↑ abnormalities in brain structure and function

6. But deficits likely reversible with extended abstinence (SLIDE 35)  

a. Change in CB1 density normalizes after 2-4wks of abstinence [27, 28]

b. Cortical blood volumes normalize

c. Especially in regions important for cognition

7. Adults (SLIDE 36)

a. Apparent after a few days of abstinence [29, 30]

b. 30-day resolution [31-38]

                        8. Unclear whether adult findings generalize to adolescents (SLIDE 37)

a. Contradictory and controversial findings

b. Some suggest no lasting deficits among abstinent adolescent users [39]

c. Most show partial recovery following sustained abstinence [40]

d. Others find deficits after 30 days of abstinence [22, 24, 41-45]

V. Unanswered Questions on Cannabis’ Impact on Adolescent Cognition (SLIDE 39)

            A. Cognitive differences pre-existing or consequence of cannabis use?

            B. Time course of cognitive recovery?

            C. Cause adverse functional outcomes?

            D. How to quantify quantity?

E. Who is most affected?      

1. Impact of comorbidities

2. Impact of varying potencies

3. Genetics

VI. Summary (SLIDE 40)

            A. Rates of cannabis use ↑ among adolescents

            B. Brain development in regions of higher-order cognition → ↑ vulnerability

            C. Clear pattern of acute cognitive effects

            D. Less clear pattern of residual effects, but reason for concern

            E. Several areas of inquiry, especially urgent because of rapid policy shifts




















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