Cannabis in psychiatry · 2020. 5. 6. · While synthetic cannabinoids are full agonists at CB1...
Transcript of Cannabis in psychiatry · 2020. 5. 6. · While synthetic cannabinoids are full agonists at CB1...
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Cannabis in psychiatry
Dr. Layali Abbasi
Psychiatrist
Al-Balqa Applied University
2019-2020
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Each species has differences in cannabinoid concentrations
Possible origins
Central Asia
Himalayan Mountains
Three subspecies
Cannabis sativa Cannabis indica Cannabis ruderalis
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Cannabinoids Δ9-tetrahydrocannabinol (THC)
Δ9-tetrahydrocannabivarin (THCV)
Cannabidiol (CBD)
Cannabinol (CBN)
Cannabigerol (CBG)
Cannabichromene (CBC)
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Appears to soften THC effectsCBD
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•Energy:
•Seed productionPollinated plant
•Energy
•Cannabinoid production
•Sinsemilla: without seeds
•High THC, no CBD
Unpollinated plant
(Sinsemilla)
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Modes of consumption
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Smoked: Rolled cigarette
Hash oil: concentrated
THC resin
Smoked
Vaped
Ingested orally
Food Usually in fat
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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
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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
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Cannabinoid Pharmacology and Synthetic Cannabinoids
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Cannabinoid pharmacology
•CB receptors
•Endogenous ligands
Synthetic cannabinoids (SCs)
•What they are and their effects
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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.
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Effects
CB1
Endogenous cannabis?
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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
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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
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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
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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)
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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
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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
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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
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Sensitivity of all the senses
Time passing more slowly
Light-headedness
Relaxation
Euphoria
Feelings of increased insight
Laughter
Enhanced emotional awareness
Acute effects
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Anxiety
Panic
Delusional thinking
Loss of control of thoughts
Memory impairment
Feeling less sociable
Negative effects
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Cognitive effects of cannabis use
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Cognition
Sustained impairment
Cannabis use beginning in adolescence
•Long-term cognitive impairment:
•8 IQ points
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Cannabis and driving
•Driving ability impaired
•Reaction time, judgement, motor coordination are poorer
•Distortion of perception of time and distance
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Impact on road traffic accidents
Cannabis
•Increase in risk: 2-3 times
Alcohol
•Increase in risk: 6-15 times
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Cannabis use and psychosis risk
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Acute cannabinoid psychosis
Paranoid or manic
Less commonly: hebephrenic features
•Posturing
•Bizarre gestures
Insight: markedly impaired
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Highest risk: Sinsemilla Synthetic cannabinoids
Risk factor for psychotic illness
Cannabis
Particular concern: heavy, daily patterns of use, beginning in adolescence
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Acute psychosis
Return to normal life
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Acute cannabis psychosis
50% Eventually long-term psychiatric patients
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Cannabis and anxiety
Cannabis can cause anxiety and panic reactions
Inconsistent findings about anxiety disorders and depression
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Approved cannabis formulations
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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
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•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
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Evidence for therapeutic use
•Chronic pain
•Nausea and vomiting related to chemotherapy
•Spasticity related to MS
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Propensity for addiction
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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
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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
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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
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THE END