Synthetic Cannabinoids


Shelley A. Holmer MD

Duke University School of Medicine

©AMSP 2013

(Slide 1)

I.     Introduction (Slide 2)

A.  Case

1.   27 yo woman who presented with

a.   Trembling

b.   Confusion

c.   Voices (auditory hallucinations)

d.   Fears people want to harm her (paranoid delusions)

2.   No family history of psychosis

3.   Medical work-up →no major medical dx

4.   Recent use of synthetic cannabinoid product, “Spice”

B.  This lecture will review (Slide 3)

1.   Background on cannabinoids

2.   Development of synthetic cannabinoids (SC)

3.   Risks associated with use

4.   Synthetic cannabinoids vs marijuana

II.   Background on cannabinoids

A.   Natural cannabinoids = marijuana[1](Slide 4)

1.   Comes from the plant Cannabis sativa

2.   Composed of > 500 compounds[2]

3.   66 compounds are "cannabinoids”

a.   Psychoactive cannabinoids (alter perception/behavior) (Slide 5)

1'.  Tetrahydrocannabinols (THC)*  (important below)
2'.  Cannabinol (CBN)
3'.  Cannabinodiol (CBDL)

b.   Non-psychoactive cannabinoids

1'.  Cannabigerols (CBG)
2'.  Cannabichromenes (CBC)
3'.  Cannabidiols (CBD)* (important below)

c.   THC and CBD have several opposing properties

B.  Cannabinoid Receptors (Slide 6)

1.   CB1 receptor

a.   Produces psychoactive effects

b.   Found in CNS (brain and spinal cord)

c.   THC = partial agonist (positive effect) of CB1

d.   CBD = antagonist of CB1

2.   CB2 receptors

a.   Found mostly in immune cells outside CNS

b.   Involved in immune function and inflammation

C.  Physiologic effects of cannabinoids

1.   Psychoactive effects (DSM-IV) (Slide 7)

a.   Euphoria

b.   Sensation of slowed time

c.   Impaired judgment

d.   Impaired coordination

e.   Social withdrawal

f.     Anxiety

g.   Psychosis (Slide 8)

1'.  ’Defined
                                                          a'.        Hallucinations +/-
                                                          b'.        Delusions
                                                          c'.        Without insight
                                                          d'.        Alert/oriented
2'.  Potential cannabinoid impact:
                                                          a'.        THC may ↑ psychosis[3]
                                                          b'.        CBD may ↓ psychosis[4]

2.   Non-psychoactive effects (Slide 9)   

a.   ↓ Nausea

b.   ↑ Appetite

c.   ↓ Pain[5]

3.   Chronic use leads to (Slide 10)

a.   Tolerance

1'.  Increased amount required for same effect
2'.  Diminished effect with use of same amount

b.   Withdrawal symptoms when stopped[6]

1'.  Symptoms include (DSM5)
                                                          a'.        Irritability/anger/aggression
                                                          b'.        Anxiety
                                                          c'.        Sleep difficulty
                                                          d'.        ↓ Appetite
                                                          e'.        Restlessness
                                                           f'.        Depressed mood
                                                          g'.        Physical symptoms (stomach pain, tremor)
2'.  Peak ~3-4 days
3'.  Resolves after ~7 days

III.  Synthetic cannabinoids (SC) for medical use (Slide 12)

A.  Dronabinol (Marinol)

B.  Nabilone (Cesamet)

C.  FDA approved for

1.   Nausea/vomiting with cancer chemotherapy

2.   AIDS associated anorexia and weight loss

IV. Synthetic cannabinoids (SC) for recreational use (Slide 13)

A.  Development: originally for research

1.   Many different compounds, JWH18 most well known

2.   Designed for medicinal use[7], [8], [9], [10], [11]

a.   ↓ Pain

b.   ↓ Nausea

c.   Glaucoma

d.   ↓ Inflammation

3.   None approved for human use

B.   Pharmacodynamics of SC compounds

1.   Full agonists at the CB1 receptor

2.   Many have higher potency than THC[12]

V.   Synthetic cannabinoids: the commercial product “Spice”

A.  Marketing (Slide 14)

1.   Street Names

a.   Spice (Frank Herbert’s Dune)

b.   K2 (world’s second highest mountain)

c.   Red magic

d.   Red dragon

e.   Diesel

f.     Serenity

g.   Blueberry Meditation

2.   Sold as herbal incense

3.   Labeled “not for human use”

B.  Production (Slide 15)

1.   Composed of SC compounds sprayed on some substance

a.   Non-psychoactive herbs such as salvia

b.   Cardboard

2.   No dose control

3.   No regulation of potentially harmful components

C.  Recognition of use (Slide 16)

1.   First seen in Europe in 2004

2.   First marketed in U.S. in 2008 

3.   In 2012: 11 % 12th grade used: 2nd most for illicit drugs[13]


D.  Recognition of medical concern (Slide 17)

1.   Increasing reports of SC by US forensic laboratories

a.   15 reports in 2009

b.   2977 reports in 2010

2.   Calls to US poison control centers

a.   2947 calls in 2010

b.   6957 calls in 2011

c.   5200 calls in 2012

3.   11,406 emergency room visits related to SC in 2010[14]

E.  Legal status of Spice (Slide 18)

1.   Banned in Europe in 2008 due to health concerns

2.   U.S. federal law: no medical use (Schedule I) 2011

3.   U.S. state law: possession illegal in 41 states

4.   But remains available

a.   Headshops (stores selling pipes, etc for cannabis users)

b.   Convenience stores/gas stations

c.   Internet

F.   Why is it popular?[15], [16]  (Slide 19)

1.   New/novel way to get “high”

2.   False belief SC safe because marketed as

a.    “Herbal”

b.   + Legal

3.   Might ↓ cannabis withdrawal

4.   Inexpensive

5.    Accessible

6.   Not detected on drug screens so ↓ legal problems for (Slide 20)

a.   Military personnel

b.   Students

c.   Athletes

d.   People on probation

e.   Employees with required drug screens

f.     Patients in drug treatment programs

VI. Risks

A.  Case (Slide 22)

1.   Pt became immobile and incommunicative

2.   Two months in hospital with psychosis

3.   One year later not using Spice and psychosis free

B.  Case reports on acute toxicity[17], [18]  

1.   Psychiatric (Slide 23)

a.   Agitation

b.   Anxiety

c.   Psychosis

1'.  Paranoia
2'.  Delusions
3'.  Hallucinations
4'.  Feeling of being stuck inside a dream

2.   Neurologic (Slide 24)

a.   Seizures

b.   Dilated pupils

c.   Jerking movements

d.   Decreased reflexes

3.   Cardiovascular (Slide 25)

a.   ↑ Heart rate

b.   ↑ Blood pressure

c.   Chest pain

4.   Gastrointestinal (Slide 25)

a.   Nausea

b.   Vomiting

c.   Diarrhea

C.  Treatment of acute intoxication17  (Slide 27)

1.   Rx anxiety and psychosis

a.   Verbal reassurance: “talk down”

b.   Medication for agitation: lorazepam 1 – 2 mg  

c.   Seclusion/restraint only if a serious danger to self

d.   Evaluate need for ongoing psychiatric care

2.   Neurologic (Slide 28)

a.   Seizure monitoring

b.   Evaluate for muscle injury → muscle destruction

1'.  Pain/weakness in muscles
2'.  Labs: ↓ kidney function

3.   Cardiovascular  (Slide 29)

a.   Monitor blood pressure and heart rate

b.   EKG

c.   Labs: heart damage enzymes

1'.  Troponin > 0.2 ng/ml
2'.  CKMB > 3 ng/ml

4.   Gastrointestinal (Slide 30)

a.   Medication for nausea

b.   IV fluids

c.   Labs: check for low potassium 2° vomiting

D.  Potential for lasting consequences

1.   Based on anecdotal data/case studies

2.   Myocardial infarction: MI or heart attacks[19]  (Slide 31)

a.   Three healthy adolescents who developed MI

b.   No personal or family history of early onset cardiac disease

c.   All smoked the SC “K2” just prior to onset of chest pain

3.   Psychosis

a.   SC ↑ psychosis if prior psychotic illness[20] (Slide 32)

1'.  15 forensic inpatients with psychotic illness
2'.  All actively taking antipsychotics
3'.  5 with relapse of psychotic symptoms
4'.  24 hours after smoking JWH-018

b.   SC may cause first episode psychosis[21] (Slide 33)

1'.  Ten men admitted psychiatrically for psychosis
2'.  No previous history of psychosis
3'.  Only one had a family history of psychotic illness
4'.  Frequency of use ranged from
                                 a’ Four uses over a 3 week period
                                 b’ Daily for 1.5 years
5'.  7/10 patients needed meds for psychosis
6'.  Three patients still had psychosis five months later

4.   Self harm/suicide while intoxicated  (Slide 33)

a.   Suicidal thoughts21

b.   Reports of self-injury[22]

E.  Risks of SC compared to natural marijuana (NM)

1.   Overdose (Slide 36)

a.   SC are sprayed onto unknown substance

1'.  No dose control
2'.  Areas of variable concentration in a single batch

b.   SC full agonist and THC partial agonist at the CB1 receptor

c.   SCs can have up to 300-fold more potency than THC

2.   NM contains CBD with potential antipsychotic effects (Slide 37)

3.   Natural marijuana may ↓ risk of seizure[23]

4.   No long-term studies on SC compounds

VII.        Conclusions (Slide 38)

A.  SC are commonly used

1.   Easy to obtain despite ban

2.   Not detected on urine tests

3.   Risks not commonly known

B.  Ask about use

C.  Tell patients about risks






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