On average, .....of Canadians (4.4 million people) over the age of 15 have used cannabis in the past 12 months
15%
15-19 years: 19%
20-24 years: 33%
25 years and
older: 13%
Cannabis Pharmacology
Consumed in many forms:
Smoked (combusted)
Vaporized
Made into oils/gummies (edibles)
Used in
cooking/baking
Concentrated into hash and shatter and then smoked
-there are 2 main active
compounds......&.......
Delta-9-Tetrahydrocanabinol (aka THC)
Cannabidiol (aka CBD)
There are also thousands of other compounds, some active, some not
THC
THC is the main psychoactive compound found in cannabis
THC-rich resins can be extracted from the cannabis plant
Shatter
Shatter is basically crystalized THC resin.
Preparation of shatter is also dangerous as it requires high
temperatures so
butane is often used
THC/SHATTER are EXTREMELY high in THC
Substance induced psychosis is a real concern here
because THC is fat soluble, it stays in the body for a long time,
making the
psychosis difficult to treat
Endocannabinoid System:
Two primary receptors in this system:(oncell surfaces)
CB1
CB2
CB1 receptors are found in the following areas in the body:
Cerebral cortex
Hippocampus
Basal ganglia
Hypothalamus
Anterior cingulate gyrus
Intrinsic and
extrinsic neurons in the GI tract
CB2 receptors are found in?
Immune system (primarily)
Blood vessel cells/blood cells
Action of CB Receptors
-Couple with G-Protein
-Activation on presynaptic cells→
reduction in release of inhibitory and
excitatory NTs
CB1 receptor:
distributed in the brain
-Reduces release of Ach, DA, GABA, glutamate, NA
- Ultimately
leads to reduction in signaling of pain
CB2 receptor:
Located on immune cells
Binding of ligand leads to reduction
in release of cytokines
Ultimately leads to regulation of the
immune system
Acute THC Intoxication
Altered, more intense senses
Impaired memory and inability
to
divide attention
Impaired body movements;
body
tremors
Changes in mood (can be more
mellow or
more elevated/anxious)
Increased appetite
Impaired
coordination/balance
Tachycardia
Hypertension
Dilated pupils and red eyes
Dry mouth/throat
With high dose or potency
cannabis or extracts- users can experience......
Hallucinations
Delusions
Psychosis
Shatter
specifically:
Burns due to high temp required to
both
create and to smoke/vaporize
Management of Acute THC Intoxication
Unintentional ingestion in children
More likely to have severe
symptoms
Hyperkinesis or deep
coma
CNS depression, including
respiratory depression is possible
Cannabinoid-Induced Hyperemesis
Syndrome
Should be on
your radar in the case
of intractable vomiting
More on
this later
Mild intoxication
Supportive care is usually all that’s
needed
Reduce
stimulation in the room
Reassure patient the symptoms will
abate
management of Severe THC intoxication with agitation
-Benzodiazepines are first line
-May need to add other
drugs
- Suspect shatter or multi-drug use
in this case
Long-Term Effects of Cannabis Use
Use before 25 years:
Has been shown to impact brain
development
Can have
long-term impacts on:
Learning processes
Thinking
Memory
Brain connections
Long-term cannabis use can also:
Impact executive functioning
Increase risk of
psychosis,
depression, and anxiety
Increase risk of lung
conditions
including COPD and worsening
asthma
Increase risk of Cannabinoid Induced
Hyperemesis
Cannabis in Pregnancy
-Primary active components: CBD and THC
- Both highly fat
soluble
- Both cross placenta and into breastmilk (~10% maternal
plasma concentration in
placenta with acute exposure, higher with
repeat exposure)
- Cannabis available now MUCH more potent in
terms of [THC] compared to 30
years ago
- Over 20% THC on
average now compared to about 2% in the 1980s
SOGC (Society of Obstetricians and Gynaecologists of Canada) position: Cannabis in Pregnancy
-most commonly used recreational drug in pregnancy in Canada
Most pregnant women (~70%) believe there is little to no risk
in
using cannabis a few times per week during pregnancy, even in
the first trimester
SOGC position: safest amount of cannabis in
pregnancy is NO
CANNABIS; “why risk it?”
Cannabis in Pregnancy: Impact on Outcomes
- In general, risk is unclear as the evidence is weak
- Use in
pregnancy may be associated with increased risk of low birth
weight
and preterm delivery
- Evidence complicated by
polysubstance use as cannabis often consumed
simultaneously with
tobacco
- Use while breastfeeding may be associated with
increased risk of
- CV or mental health issues
- Learning
development and behaviour issues
What is Cannabinoid-Induced
Hyperemesis Syndrome (CIHS)?
“Cannabinoid Hyperemesis Syndrome is characterized by chronic
cannabis use, cyclical episodes of nausea and
vomiting, and
frequent hot bathing.”
Symptoms of CIHS
what are the 3 phases?
3 Phases:
Prodrome-normal eating habits/continued cannabis
use. Hyperemesis-nausea/vomiting/compulsive hot showers/ abdomina
pain
Recovery(follows active or supportive mgt)-restored aeting
habits, relative wellness
Prodromal Phase
abdominal discomfort, early morning nausea, and anxiety
about
vomiting.
This phase can last months to
years.
Patients usually continue cannabis use and may increase
it’s used due to the belief
that cannabis will help with their nausea
Hyperemesis Phase
episodes of nausea and vomiting.
Intractable and renders the patient incapacitated.
Patients
can vomit profusely up to 5 times per hour.
Accompanied by
abdominal pain.
Can last for hours to days.
Marked
weight loss (>5kg) and dehydration are common
Learned
behaviour of multiple hot showers per day to alleviate nausea and
vomiting
Recovery Phase
all symptoms are mostly or completely resolved.
Return to
normal appetite and eating
Restoration of normal body
weight
Restoration of normal bathing habits
Clues in the Diagnosis of CIHS
The patient frequently uses cannabis or cannabinoids
Symptoms are relieved by a hot shower or bath
Symptoms are eliminated when cannabis/cannabinoid use ceases
Age <50 y/o is most common
Significant weight loss (>5kg)
Symptoms are worst in the morning during a hyperemesis episode
All lab tests, radiography, and endoscopy tests lack significant findings
Bowel activity is normal
Rome IV Diagnostic Criteria for CIHS
-Must include all of the following:......
-Criteria fulfilled for the last 3 months with symptom onset at
least 6 months
before diagnosis
-Supportive remarks:
May be associated with pathologic bathing
behavior (prolonged hot baths or
showers).
1. Stereotypical episodic vomiting resembling cyclic vomiting
syndrome (CVS) in
terms of onset, duration, and frequency
2. Presentation after prolonged excessive cannabis use
3.
Relief of vomiting episodes by sustained cessation of cannabis use
Proposed Pathophysiology
Dysregulation of the endocannabinoid system
Genetic
variation in metabolism of cannabinoids
Altered
thermoregulation and GI motility by the endocannabinoid
and
endovanilloid systems
Primary receptor involved =
TRVP1
Present on skin and in GIT
Long term exposure of
TRVP1 to cannabinoids can inactivate the receptor
Leads to
reduced gut motility→ nausea→ vomiting
Why all this talk about hot showers?
-The endocannabinoid system is involved in many different processes
in the body
- CB1 receptors in the hypothalamus play a role in
thermoregulation
- Cannabinoids cause a dose-dependent reduction
in heat production
- Very high doses can lead to hypothermia and
nausea/vomiting
- Diversion of blood from GIT to skin to cool
down→ reduced N/V
- Hot showers (and capsaicin) work on both the
endocannabinoid and
endovanilloid systems together, increasing
gut motility
trtment with hot showers or capsaicin
1. prolonged exposure to cannabinoids inactivates the TRPV1 receptor.
2.TRPV1 inactivation leads to nausea and emesis both via central effects and vagal afferents.
3.TRPV1 inactivation alters gastric motility.
4.cutaneous heat or capsaicin exposure normalizes gastric motility via activation of TRPV1
Evidence for Treatments:
The only treatment that has consistently been shown to work is
cannabis
cessation and this paper reinforced that.
a new pilot study by dean et al.
Not amazing
Well done but still a pilot
30 mins may be
too soon to see benefit
Overall, trial shows trend to benefit
of treatment with capsaicin
DSM-V Criteria: Substance Use Disorder
“A problematic pattern of [substance] use leading to
clinically
significant impairment or distress, as manifested
by at least 2
of the following, occurring within a
12-month
period:”
-Impaired control
- Social
impairment
- Risky use
- Pharmacological criteria
Diagnosis of Cannabis Use Disorder
A problematic pattern of cannabis use leading to clinically
significant impairment or distress, as
manifested by at least two
of the following, occurring within a 12-month period:
1. Cannabis
is often taken in larger amounts or over a longer period than was
intended.
2. There is a persistent desire or unsuccessful efforts
to cut down or control cannabis use
3. A great deal of time is
spent in activities necessary to obtain cannabis, use cannabis, or
recover from its
effects.
4. Craving, or a strong desire or
urge to use cannabis.
5. Recurrent cannabis use resulting in a
failure to fulfill major role obligations at work, school, or
home.
6. Continued cannabis use despite having persistent or
recurrent social or interpersonal problems caused or
exacerbated
by the effects of cannabis.
7. Important social, occupational, or
recreational activities are given up or reduced because of cannabis
use.
8. Recurrent cannabis use in situations in which it is
physically hazardous.
9. Cannabis use is continued despite
knowledge of having a persistent or recurrent physical or
psychological
problem that is likely to have been caused or
exacerbated by cannabis.
10. Tolerance, as defined by either of
the following:
a) A need for markedly increased amounts of
cannabis to achieve intoxication or desired effect.
b) Markedly
diminished effect with continued use of the same amount of
cannabis.
11. Withdrawal, as manifested by either of the
following:
a) The characteristic withdrawal syndrome for cannabis
(refer to Criteria A and B of the criteria set for
cannabis
withdrawal, pp. 517–518).
b) Cannabis (or a closely
related substance) is taken to relieve or avoid withdrawal symptoms.
Treatment of Cannabis Use Disorder
Non-pharmacological treatments:
Drug/addiction counseling
CBT
Motivational
interviewing
Mutual help groups (e.g. Narcotics Anonymous)
Pharmacological treatments:
A few have been studied, to varying degrees of success:
-
Gabapentin
- N-acetylcysteine (NAC)
- Nabiximols
-
Cannabidiol
- Lots of others (topiramate, antidepressants,
divalproex, atomoxetine, dronabinol, etc)
have largely been found
to be no better than placebo
Gabapentin for Cannabis Use Disorder
-Thought to work in the amygdala and nucleus acumbens to help restore
GABA
tone to normal levels
-Considered an anti-craving
agent
- Has evidence for use in alcohol use disorder as an
anti-craving agent,
especially in addition to naltrexone.
-
Evidence in cannabis use disorder is mixed.
N-Acetylcysteine for Cannabis Use
Disorder
Antioxidant precursor to glutathione
Impacts glutamate
functioning in the brain
Thought to impact cannabis use
disorder by:
Correcting glutamate dysregulation in the nucleus
acumbens as a result of
substance use
Upregulating the
glutamate transporte GLT-1
Thus removing excess glutamate from
the nucelus acumbens
Evidence has been mixed at best
Harm Reduction Measures for Cannabis Use
-any form of weed poses risks to your health.
-the earlier u begin the greater the risk start later in life.
-choose low strength prdts
-dont use synthetic cannabis products.
-smokin joints is harmful-to your lungs
-do not inhale or hold your breath
-limit use as much as possible
-weed use impairs your ability to drive.
-pple wit psychosis in their fam or pregnant shd not use
-avoind combining any of the risky behaviours-they increase the chances of harming your health.