Cannabis in psychiatry

Dr. Layali Abbasi

Psychiatrist

Al-Balqa Applied University

2019-2020

Each species has differences in cannabinoid concentrations

Possible origins

Central Asia

Himalayan Mountains

Three subspecies

Cannabis sativa Cannabis indica Cannabis ruderalis

Cannabinoids Δ9-tetrahydrocannabinol (THC)

Δ9-tetrahydrocannabivarin (THCV)

Cannabidiol (CBD)

Cannabinol (CBN)

Cannabigerol (CBG)

Cannabichromene (CBC)

Appears to soften THC effectsCBD

•Energy:

•Seed productionPollinated plant

•Energy

•Cannabinoid production

•Sinsemilla: without seeds

•High THC, no CBD

Unpollinated plant

(Sinsemilla)

Modes of consumption

Smoked: Rolled cigarette

Hash oil: concentrated

THC resin

Smoked

Vaped

Ingested orally

Food Usually in fat

First-episode psychosis patients vs healthy controls

High potency cannabis: 5x more likely to suffer a psychotic disorder

Hashish use: not related to increased risk of psychosis

• Lower THC content, presence of CBD

Sinsemilla

• Highest risk of psychotic disorder

• South London: ¼ of new cases of psychotic illness

Cannabis is subdivided into three species: C. sativa, C. indica, C. ruderalis

•Each species has differences in cannabinoid concentrations

Sinsemilla is a very potent product. It is high in THC and has no CBD

•CBD appears to soften the effects of THC

Sinsemilla use is associated to higher risk of psychosis than hashish

THC

Key Points

Cannabinoid Pharmacology and Synthetic Cannabinoids

Cannabinoid pharmacology

•CB receptors

•Endogenous ligands

Synthetic cannabinoids (SCs)

•What they are and their effects

By the early 1990s, the molecular biology of cannabis was worked out. There were receptors on neurons, termed CB1 receptors. This is where THC was producing its effects. If a receptor for a drug like THC exists in the body, there are likely to be natural cannabis molecules as well. These were soon discovered.

?

Effects

CB1

Endogenous cannabis?

The brain has a natural cannabinoid system, or endocannabinoid system. Since then, it has become clear that the endocannabinoid system is involved in neuronal communication, plasticity and learning in neuronal networks

Effects

CB1

Endocannabinoid system

•Neuronal communication•Plasticity •Learning

Cannabinoid CB1 receptors are expressed mainly in the CNS and mediate many of the psychoactive effects of cannabinoids.There is another receptor, the CB2 receptor, which is expressed mainly in the immune system and in blood cells.

CB1

CB2

CB1 receptorsExpressed in the CNSPsychoactive effects

CB2 receptorsExpressed in immune system and hematopoietic cells

AEA

CB receptors

The exogenous cannabinoid agonists, such as THC do not recreate the fine-grained effects of the endogenous cannabinoids. The spatial and time profile of endogenous cannabinoid signaling is tightly controlled.

In contrast, THC administered exogenously floods the system indiscriminately. Network functions such as information processing and memory are disrupted by exogenous CB1 agonists such as THC. Adverse effects on network dynamics underlie the psychological effects of cannabinoids.

Exogenous ligands (THC)

Disruption of network functions

• Information processing

•Memory

Synthetic cannabinoids have been called “legal highs”. This includes a range of substances that can be purchased online and were initially produced by research laboratories exploring potential medical uses.

Sprayed onto cannabis plants

Full agonists

“Legal” highs

•Originally developed by research labs

• HU-210 (Hebrew University)• JWH-018 (JW Huffmann)

• Spice• K2

Synthetic cannabinoids (SCs)

While synthetic cannabinoids are full agonists at CB1 receptors, THC is known to be a partial agonist. As such, the synthetic cannabinoids impact upon this cannabinoid CB1 receptor with much greater force, and produce a correspondingly much greater effect on the psyche. These molecules are even stronger than sinsemilla

Synthetic cannabinoid: full agonist

THC: partial agonist

Greater effect

Tachycardia, palpitations and chest pain can be associated features pointing to the correct diagnosis.

Psychosis attributable to synthetic cannabinoids

•Catatonic posturing

•Bizarre behavior

•Grandiosity

•Persecutory ideation

•Disinhibition

•Aggression

SCs are not detectable in standard urine screens

Associated features

•Tachycardia, palpitations, chest pain

SCs may overwhelm the effects of APs

Smoked cannabis

•Effects appear after a few minutes

•Last 2-3 hours

Eaten cannabis

•Effects can appear after 2 hours

•Last up to 8 hours

Sensitivity of all the senses

Time passing more slowly

Light-headedness

Relaxation

Euphoria

Feelings of increased insight

Laughter

Enhanced emotional awareness

Acute effects

Anxiety

Panic

Delusional thinking

Loss of control of thoughts

Memory impairment

Feeling less sociable

Negative effects

Cognitive effects of cannabis use

Cognition

Sustained impairment

Cannabis use beginning in adolescence

•Long-term cognitive impairment:

•8 IQ points

Cannabis and driving

•Driving ability impaired

•Reaction time, judgement, motor coordination are poorer

•Distortion of perception of time and distance

Impact on road traffic accidents

Cannabis

•Increase in risk: 2-3 times

Alcohol

•Increase in risk: 6-15 times

Cannabis use and psychosis risk

Acute cannabinoid psychosis

Paranoid or manic

Less commonly: hebephrenic features

•Posturing

•Bizarre gestures

Insight: markedly impaired

Highest risk: Sinsemilla Synthetic cannabinoids

Risk factor for psychotic illness

Cannabis

Particular concern: heavy, daily patterns of use, beginning in adolescence

Acute psychosis

Return to normal life

Acute cannabis psychosis

50% Eventually long-term psychiatric patients

Cannabis and anxiety

Cannabis can cause anxiety and panic reactions

Inconsistent findings about anxiety disorders and depression

Approved cannabis formulations

Drug (Brand name) Molecule

Dronabinol (Marinol) Synthetic Δ9-THC

Nabilone (Cesamet) Synthetic cannabinoid

FDA-approved products

●Anorexia associated with weight loss in patients with AIDS

Nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments

•Oral spray

•1:1 ratio THC/CBD

•Approved in many EU countries, Canada and Latin America

•Indication:

•Spasticity treatment in multiple sclerosis

Sativex CBD THC

Evidence for therapeutic use

•Chronic pain

•Nausea and vomiting related to chemotherapy

•Spasticity related to MS

Propensity for addiction

Cannabis

Previously: no propensity for addiction?

Evidence from animal studies

•THC can be addictive

About 10% of cannabis users meet criteria for cannabis use disorder

Sinsemilla: even more propensity for addiction

Cannabis withdrawal syndrome

Resembles nicotine withdrawal

Cravings and psychomotor agitation

•Peak at days 3-4

•Diminish over 14 days

If the patient can manage abstinence for 2-3 weeks

Cravings subside

Many patients who sustain abstinence can make a significant

recovery

Scant evidence base

Psychological therapies

•May be effective for the individual

•Lack of convincing evidence

Therapeutic relationship

•Focus on motivation

Treatment of cannabis use disorder

THE END