Toxicology of Tetrahydrocannabinol (THC – The Active Ingredient in Marijuana)

1
Toxicology of Tetrahydrocannabinol(THC The
Active Ingredient in Marijuana)
2
History of Marijuana Use

• Marijuana use has been around since ancient times
  dating back in Chinese medical compendium
  traditionally dating from 2737 B.C.
• Following its use in China it spread to India and
  North Africa, and reached Europe as early as 500
  A.D.
• During 1850 to 1942 A.D. it was prescribed by the
  United States Pharmacopeia for
• Labor Pains
• Nausea
• Rheumatism
• A campaign conducted in the 1930s sought to
  portray Marijuana as a powerful and addictive
  substance.
• Many considered it the gateway drug
• In the 1960s the drug was used as a sign of
  rebellion against authority

3
History of Marijuana Use

• Controlled Substances Act of 1970 classified
  marijuana along with heroin and LSD as a Schedule
  I drug
• Schedule I Drug Highest Abuse Potential and No
  Medical Use
• Most marijuana came from Mexico until 1975
• This is when Mexico agreed to eradicate the crop
  by spraying it with an herbicide.
• Following this Columbia became the main supplier
• Following Reagan and Bush, harsher sentences and
  a crack down on importation across the border
  leads to increased domestic growth
• Especially in California and Hawaii
• There was a decreased smoking trend that didnt
  start to increase until the 1990s, but leveled
  off at levels lower than previously seen
• The History of Marijuana Use is information
  collected from source 1.

4
THC Background

• Tetrahydrocannabinol (THC) A compound,
  C21H30O2, obtained from cannabis or made
  synthetically, that is the primary intoxicant in
  marijuana and hashish. (Source 6)
• It can be seen as a crystalline structure on the
  plant as seen on the right.

5
Pharmacology of THC

• THC typically functions by binding a particular
  receptor in the brain, the Cannabinoid Receptor
  (CB1).
• The presence of this receptor indicates that
  there is a naturally occur (endogenous) ligand,
  Anandimide, as well as other related compounds.
• The response can affect the hippocampus and
  hypothalamus
• Hippocampus A complex neural structure (shaped
  like a sea horse) consisting of grey matter and
  located on the floor of each lateral ventricle
  intimately involved in motivation and emotion as
  part of the limbic system has a central role in
  the formation of memories.
• Hypothalamus A region of the brain, between the
  thalamus and the midbrain, that functions as the
  main control center for the autonomic nervous
  system by regulating sleep cycles, body
  temperature, appetite, etc., and that acts as an
  endocrine gland by producing hormones, including
  the releasing factors that control the hormonal
  secretions of the pituitary gland.
• Pituitary Gland The master endocrine gland
  affecting all hormonal functions.
• This information is from source 2, and the
  definitions are from source 4 (hippocampus) and
  source 5 (hypothalamus).

6
Neurological Effects of THC

• Endocannabinoid Synaptic Transmission
• Excitatory transmission of the neurotransmitter
  glutamate causes an influx of Ca into the
  post-synaptic neuron.
• The presence of Ca post-synaptically causes the
  production of endocannabinoids in the
  post-synaptic neuron.
• Endocannabinoids Anandamide is an example.
  Anandamide is found in chocolate, along with
  inhibitors of the enzyme that breaks down
  Anandamide. This leads to a mild euphoria
  feeling associated with chocolate consumption.
• The endocannabinoid is then released into the
  synaptic cleft.

7
Neurological Effects Continued

• Endocannabinoid Synaptic Transmission Continued
• In the synaptic cleft the endocannabinoid binds
  to the Cannabinoid Receptor of the pre-synaptic
  neuron.
• This in turn modulates neurotransmission
  pre-synapticly
• Post-Synaptic Neuron ? Pre-Synaptic Neuron
  (Renegade Transmission)
• This mechanism is reverse of what is typically
  seen
• Pre-Synaptic Neuron ? Post-Synaptic Neuron
  (Normal Transmission)
• The Neurological Effects are from source 2.

8
Normal Functions Associated With Cannabinoid
Receptor (CB1)

• Many Cannabinoid Recpetors are found in the parts
  of the brain that affect
• Pleasure
• Memory
• Thought
• Concentration
• Sensory and Time Perception
• Coordinated Movement
• This information is from source 3.

9
Toxicity of THC

• Merck Index (12th Edition) has indicated an LD50
  value for THC as determined using rats
• Male Rats were determined to have an LD50 of 1270
  mg/kg
• Female Rats were determined to have and LD50 of
  730 mg/kg
• Doing a direct scale up of this is 50g (female)
  and 86g (male) for a 68kg (150lbs) person.
• This does not, however, correlate directly with
  human toxicity and may be different.
• This information is from source 2.

10
Negative Effects of THC (pg. 1)

• Short-term effects can lead to problems with
• Memory and Learning
• Distorted Perception
• Difficulty in Thinking and Problem Solving
• Loss of Coordination
• Increased Heart Rate
• Long-term effects can lead to
• An increase in activation of the stress-response
  system
• Changes in activity of nerve cells containing
  dopamine
• Dopamine involved in regulation of motivation
  and reward

11
Negative Effects of THC Continued (pg. 2)

• Effect on Heart
• Risk of heart attack more than quadruple in first
  hour after smoking marijuana.
• Possibly from the effects on blood pressure,
  heart rate, and reduced oxygen-carrying capacity.
• Effect on Lungs
• Infrequent abuse can cause burning and stinging
  of the mouth and throat, often a cough
  accompanies this.
• Similar respiratory problems to tobacco smokers
• Daily Cough and Phlegm Production
• Frequent Acute Chest Illness
• Heightened Risk of Lung Infections
• Greater Tendency to Obstructed Airways
• Increased likelihood of developing cancer of the
  head or neck
• Evidence suggests that smoking marijuana doubles
  or triples the risk of these cancers

12
Negative Effects of THC Continued (pg. 3)

• Effects on Lungs Continued
• Marijuana smoke contains 50 to 70 percent more
  carcinogenic hydrocarbons than does tobacco
  smoke.
• Marijuana users usually inhale more deeply and
  hold their breath longer than tobacco smokers do.
• This increases the lungs exposure to the
  carcinogenic smoke.
• Effects on Immune System
• THC impairs the immune systems ability to fight
  disease
• In lab experiments that exposed animal and human
  cells to THC or other marijuana ingredients,
  normal disease-preventing reactions of key immune
  cells were inhibited
• Other studies indicated that mice exposed to THC
  or related substances were more likely to develop
  bacterial infections and tumors.

13
Negative Effects of THC Continued (pg. 4)

• Effects of Heavy Marijuana Use on Learning and
  Social Behavior
• Can Cause
• Depression
• Anxiety
• Personality Disturbances
• Can Lead To
• Falling Behind in Accumulating Intellectual, Job,
  or Social Skills
• Someone who smokes marijuana every day may be
  functioning at a reduced intellectual level all
  of the time.
• Research has shown that marijuana abusers remain
  impaired for a week after quitting, but could
  return to normal within 4 weeks.
• Some cognitive abilities may be restored, even
  after long-term heavy use.

14
Negative Effects of THC Continued (pg. 5)

• Working Associated Effects
• Increased Absences
• Increased Tardiness
• Increased Accidents
• Increased Worker Compensation Claims
• Increased Job Turnover
• Important Measures of Life Achievements that are
  Effected
• Cognitive Abilities
• Career Status
• Social Life
• Physical Health
• Mental Health
• The List of Negative Effects are all from the
  National Institute on Drug Abuse, National
  Institutes of Health, and the U.S. Department of
  Health and Human Services, Source 3.

15
Positive Effects of THC (pg. 1)

• Benefits
• Cancer or AIDS treatment
• Ability to increase appetite and decrease nausea
• Possible tumor reduction
• Glaucoma
• Decrease pressure in the eye
• Multiple Sclerosis
• Can relieve spasms

16
Positive Effects of THC Continued (pg. 2)

• Benefits Continued
• Tourette Syndrome
• Can reduce nervous tics and urges (using
  synthetic THC)
• Alzheimers Disease
• Inhibition of Plaque Formation (using high in
  vitro concentrations of THC)
• Multiple Sclerosis, Parkinson's Disease, and
  Alzheimers Disease
• Activation of CB1 receptors may facilitate
  neurogeneration and neuroprotection.
• This information is from source 2.

17
References

• History of Marijuana Use. lthttp//www.infoplease.c
  om/ce6/sci/A0859487.htmlgt
• Tetrahydrocannabinol. lthttp//en.wikipedia.org/wik
  i/Tetrahydrocannabinolgt Wikipedia
• Marijuana lthttp//www.drugabuse.gov/PDF/InfoFacts/
  Marijuana06.pdfgt National Institute of Drug Abuse
• Hippocampus lthttp//dictionary.reference.com/brows
  e/hippocampusgt Dictionary.com
• Hypothalamus lthttp//dictionary.reference.com/brow
  se/hypothalamusgt Dictionary.com
• THC lthttp//dictionary.reference.com/browse/THCgt
  Dictionary.com

18

• Information collected by and compiled by
  Nicholas Card