Gideon Koren MD FRCPC FACMT

Motherisk Israel

Ariel University

Declaration GK does not have any conflict of interest related to this

presentation

Case An 18 yr. young man drove on his bikes at 2 am

He crossed a street and was hit by a car

The driver said that the biker “just appeared from nowhere”

The biker sustained severe and debilitating brain damage

Had high blood levels of THC

Case (2)Cannabis significantly impairs:

Judgement

Motor coordination

Reaction time

Direct relationship between THC conc. and driving ability

The Big Bang November 2012: Voters in Washington legalized

nonmedical (retail) cannabis for people >21yr(Initiative 502)

Markets opened in July 2014

Serious concerns among parents and pediatricians about the impact on large numbers of adolescents

Cannabis Abstinence and Improved Memory (J Clin Pshiciatr 2018)84 adolescents-young adults

Regular users of cannabis

Randomly assigned: d/c cannabis (with TDM) or

continuation

Improved verbal memory

No effect on attention

Blevins 2018 No significant differences pre- and post policy in

rate of use

Significant post-policy increased rate of problem and use disorder symptoms

No significant increases in norms, attitudes, or perception of risk.

No evidence of post policy increase in heavy-using adolescents’ rates

Increasing cannabis potency and adolescent health Epidemiological evidence: increased cannabis

potency=

Increased risk of psychosis

Decreased spatial working memory and prose recall

Increased reports of severity of cannabis dependence

N-Acetylcysteine in THC-Dependent Adolescents RCT n=116

NAC 1200mg or Placebo twice daily plus brief counseling

8 weeks

NAC associated w OR 2.4(1.1-5.2) for negative urine THC

Effect via glutamate modulation in the nucleus accumbens

Cannabis and Adolescent Suicidality Attempts N= 86,254

Student Health Survey

21 countries

Past 30 day Cannabis use: 2.8%

0.5% in Laos, 37.6% in Samoa

Past 30 day Cannabis use: OR 2.03 (1.4-2.9) for suicide attempts

Lifetime Cannabis use: OR 2.3 (1.7-3.0) for suicide attempts

Parental THC and Offspring Use THC initiation measured in Montreal at grades

7,9,11

At grade 6: 1.8-2.8 more likely to initiate if their parents were using in the past year.

Children of Cannabis users are more likely to use THC.

Cannabis and Early Sexual Initiation N=7664

The 2015 Youth Risk Behavior Surveillance Survey

Prevalence of ESI: 15.3%

Among THC users before age 15:

OR 4.2-6.7 for ESI

OR 9 among boys, 2.8 among girls

Mental health symptoms and Marijuana in Adolescents N=527 adolescents in routine care

N=146 affirmed first yr. use of THC

Questionnaire: Associations with THC:

Anxiety

Paranoia

Hallucinations

Depression

SES

Mental health symptoms and Marijuana(2) Hallucinations: 40(27.4%)

Paranoia or anxiety: 49( 33.6%)

At least one symptom: 63(42.9%)

Monthly or more use: 70(47.9%)

More symptoms among frequent users, meeting criteria for cannabis use disorder

Strong association between adolescent THC and poor adults outcome (JAMA Pediatr 2018)

“One time cannabis use may alter teen brains” J Neurosci, Jan 14, 2019

47 adolescents reporting using Cannabis only once or twice

Increase in grey matter volume.

“We don’t really know for sure why. We also don’t know ….if its because of the cannabis, or they could have preceded the cannabis”(Garavan)

Meta analysis: Depression 37 studies including 23, 317 individuals

OR for developing depression for cannabis users:

1.37(CI 1.16- 1.62)

Suicidal ideation: OR 1.5(1.11-2.03)

Suicide attempts: OR 3.46( 1.53-7.84)

No increased risk for anxiety.

(JAMA Psyciatr 2019; 76:426-434

Authors do not discuss the Chicken and Egg effect

Discussion(1) Increasing number of studies showing long term

psychiatric morbidity among adolescents using cannabis.

Claiming that cannabis causes this morbidity.

Strongly suggesting action to reduce cannabis use.

Is it possible that kids starting cannabis earlier are more prone to psychiatric morbidity because of the very fact that they experiment early(i.e. it is part of their personality?)

Discussion(2) Tonkins (2002):(Paediatr Child Health)

Nonusers(%) Users(%)

1st Sexual intercourse 7 57

Physical fights 22 47

Weapon in school 5 19

Riding w drunk driver 12 50

Driving under influence 9 71

Discussion(3) It is not likely that cannabis causes the excess

psychiatric morbidity

It is much more likely that the premorbid personality of adolescent cannabis users render them much more likely to exhibit and suffer from psychiatric disorders.

Use of cannabis is a marker of premorbid psychiatric morbidity.

Don’t deal with the cannabis- intervene with the kid!

Effect of Cannabis on Adolescent Brain (Jacobus and Tapel)

“It remains unclear whether such disadvantages reflect pre-existing differences that lead to increased substance use and further changes in brain architecture and behavioral outcomes”

Cannabidiol in Severe Pediatric Epilepsies Studies in children suffering from Lennox-

Gestaut Syn. And Dravet Syn.

Uncontrolled by concommitant anti-epileptics

Total of 4 trials with 550 patients

Pooled average difference in seizure frequency: 20% better in CBD than in Placebo(p=0.001)

Drugs, 2018:78:1791-1804

Effectiveness of Medical Cannabidiol in Children with Autism To alleviate aggression, self- harm, restlessness, sleep

problems, hyperactivity, anxiety and other comorbidities.

Conventional treatment includes various psychotropic medications such as atypical anti psychotics, selective serotonin reuptake inhibitors (SSRI's), stimulants and anxiolytics - often not effective, and associated with adverse drug reactions.

With initiation by their parents and support from their MDs, increasing numbers of children with ASD receive approval for cannabis products to combat autistic symptomatology.

Barchel et al, 2019* 53 children , median age of 11 (range 4-22) yr. received cannabis and were followed up for changes in ASD-related symptoms (3). *Median treatment 66 days (range30-588),Median daily CBD and THC doses were 90 mg (range: 1.5 – 315) and 6.75 mg (range: 0.5-49.5) mg, respectively. * Self-injury and rage attacks, reported among 34 patients, were improved in 23 (67.6%), after the administration of cannabidiol.

Results(2) * Hyperactivity symptoms (n=30) improved in 21

(70%) and sleep problems(n=21)- improved in 15 (71.4%).

*Anxiety and mood problems (n=17) improved in 8 patients (47.1%) and social Communication and reciprocity issues (n= 15) improved in 13 patients ( 86.7%).

*Overall change in ASD symptoms, significant improvement was reported in 43.1%, mild to moderate improvement was reported in 31.4, and no change was reported in 21.6% with worsening in two (3.9%). The most common reported adverse effects were somnolence, nausea, and change in appetite.

Cannabis for FASD Fetal Alcohol Spectrum Disorder (FASD) has been

recently estimated to afflict up to 5% of American children.

Most of these children exhibit different degrees of symptomatology of disruptive behaviors.

Yet, there has been very little research on the efficacy and safety of pharmacological modalities, limited mostly to stimulants for ADHD, or second generation atypical antipsychotics for aggression

Cannabis for FASD(2) Five cases(3 children, 2 young adults) were diagnosed

by us in recent years as suffering from FASD.

At the time of diagnosis none of them received cannabinoids. In all cases, the initiation of cannabinoid use was by the parents. Three of them received cannabidiol and two received THC.

). Disruptive symptomatology was ranked by the parent version of the Nisonger Child Behavior Rating Form (N-CBRF), a Visual Analog Scale (VAS) for disruptive symptom.

ResultsChanges in disruptive symptoms before

vs. after cannabis use were quantified by Student’s t test for paired data.

In all 5 cases there was a highly statistical decrease in the disruptive behavior score from 18+/- 1.0 prior to cannabis use to 6+/-2.1 following introduction of cannabis (p=0.0002).