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Medical Marijuana: Toxicity of Tetrahydrocannabinol (THC)

Updated on July 10, 2012

Median Lethal Dose of THC (LD50) in Humans

Median lethal dose in humans still cannot be substantiated, several studies tried to assess a mean valute, however body weight, THC content of the cannabis plant and the method of intake makes this calculation difficult to perform. However, two types of calculations may provide an estimated amount of 1500 pounds of marijuana smoked all at once.

Some studies claim that the interval for new users may vary between 2.5 - 120 milligrams, other studies claim values between 15 - 60 mg. Another data suggests that threshold for psychological effects depends strongly on how the user ingests tetrahydrocannabinol. Generally if thc is inhaled, a single dose carry 2-3 mg of thc inside the body.

Tolerance and maximum daily dosage

Another considerable factor is development of tolerance in heavy users, this means their body becomes more resistant and less sensitive to psychotropic effects, a study conducted in Jamaica reported a mean daily intake of 24,5 g of cannabis, this equal to approximately 1000 mg of THC.

Median Lethal Doses in Animals

  • Rats (Depending on sex and strain) : 800-1900 mg/kg
  • Dogs: 3000 mg/kg
  • Monkeys: 9000 mg/kg

Tetrahydrocannabinol (THC) also known as delta-9-tetrahydrocannabinol is the main psychoactive component of the cannabis plant also known as marijuana whereof several urban attributes are given, some of the most popular are pot, ganja and weed. THC was first isolated in 1964 by Israeli chemist Raphael Mechoulam.

The molecule's main characteristics represent marked psychotropic properties such as:

  • euphoria,
  • anxiety,
  • alterations in sensory perception,
  • impairments in memory,
  • psychomotor performance.

A notable amount of scientific studies showed possible toxic properties associated with intake of thc.

These bad effects are mainly presented on a psychological basis where tests measuring cognitive skills such as memory, attention and problem-solving abilities were and are still regarded as an important starting point for scientists to have a closer look to short- and long-term effects of cannabis on human brain.

However, these results may show inaccurate data since this psychoactive molecule causes subjective effects and even from a greater population, accurate data cannot establish a possible fact that THC has only detrimental effects to be considered.

Since the application of medical marijuana in chronic patients has gained a remarkable trend in home remedies for symptomatic relief from painful chronic or acute conditions, THC has been shown to play a very useful role in fast and instant relief.

Is There a Connection Between THC's Toxic Effects and Unwanted Negative Mental and Physical Effects?

Knowing that THC is not the only substance to generate benefits but also its counterpart CBD also present in the plant, it has been reported that THC causes undesirable effects like paranoia, axiety and even panic attacks in users with a family history of mental illnesses and disorders such as schizophrenia or panic disorders. Meanwhile, physical effects in inexperienced, fatigued or currently physically ill users may cause unwanted symptoms of chest tightness, difficulty breathing, lightheadedness and syncope.

Adverse Effects Showed In a Table From a Clinical Trial Conducted in California in the 1970s
Adverse Effects Showed In a Table From a Clinical Trial Conducted in California in the 1970s | Source

Dosage, Setting and Molecular Ratio

Apart from recreational purposes, medical application of cannabis requires a personal setting in every patient requesting this additional therapy relatively to dosage, body weight, previous habits of cannabis usage and another factor that is often forgotten, the strain and THC/CBD ratio of the plant itself from which the bud is harvested.

Illustration showing the region where the hippocampis is located.
Illustration showing the region where the hippocampis is located.
Microscopic pictures showing DNA breakage in hippocampal neuronal cells. Thin arrows show condensed chromatin, while the thick ones show normal chromatin.
Microscopic pictures showing DNA breakage in hippocampal neuronal cells. Thin arrows show condensed chromatin, while the thick ones show normal chromatin. | Source

Is THC Bad For The Brain?

THC is a lipophilic molecule meaning that it "likes binding to lipid-derived molecules", this allows tetrahydrocannabinol to pass through the blood-brain barrier and reach the brain. It is known that THC reaches peak levels fifteen minutes after inhalation. Among the bad effects - both short- and long-term - of marijuana, the most researched negative characteristics are short-term memory impairments and long-term memory deficits and information processing difficulties.

Hippocampal Neurotoxicity

In 1998 a prestigious study conducted by Greenwood et al revealed that acute effects of THC may cause hippocampal cell death. With particular laboratory methods of cell conservation and staining, scientists measured cell viability over a period of several weeks. These cell cultures were obtained by previously decapitated rat pups, which were injected with THC.

Nuclear Contraction and DNA Breakage

It has been shown that hippocampal neuronal cells while treated with THC suffer a damage to their nuclues and DNA, two types of neuronal cells CA1 and CA3 pyramidal cells had an approximately 50% smaller nucleus compared to those in control group. This phenomenon may explain the memory deficits measured in humans cannabis smokers.

THC Generates Free Radicals

THC is a partial agonist of CB1 receptors that is THC after passing the blood-brain barrier activates a cascade of reactive pathways by partially binding to this kind of receptor. A strong literature have found that the chemical pathways triggered by THC are reactive inflammatory enzymatic responses.
The major enzymes found to be the core cause of neurotoxicity are COX and PLA-2. These enzymes are involved in inflammatory processes usually provoking cell death stressing the point that thc may be associated with depression.

Illustration showing THC-induced pathway leading to cell death.
Illustration showing THC-induced pathway leading to cell death. | Source
Mitochondrial organelles are shown in orange with a special fluorescent staining method.
Mitochondrial organelles are shown in orange with a special fluorescent staining method. | Source

Is THC Toxic For The Lungs?

In 2005 a study conducted by Sarafian et al measured the mitochondrial activity of epithelial lung cells in mice. The purpose was to determine if inhaled or in other terms smoked THC is toxic to lung cells, and by this down regulates the energetic processes of those cells.

The results showed impaired mitochondrial functioning in groups receiving only cannabis smoke and cannabis combined with tobacco smoke. This means that even if the study was performed on rats, the negative effects of THC may also be an important danger in human alveolar epithelial cells.

After alcohol, cannabis and benzodiazepines are the second most frequently detected substances from blood samples of impaired drivers or drivers who caused a car accident.

Does THC in Cannabis Affect Driving?

With its psychoactive effects such as impaired psychomotor function, cognitive impairment and perception. These impairments may also get worse if combined with a specific medication, other types of drugs or alcohol.

Contrasting scientific evidence showed little or no correlation between thc intoxication and driving skills.

If so, how can we explain car accidents resulting from cannabis intoxication? Does the media broadcast and print credibly? Or is it just false data to promote anti-drug campaign?

An interesting point stressed the question whether acute THC effects manifest different and/or greater ability impairments in infrequent users than those who smoke regularly and relatively heavy amounts. Statistical data showed significant differences among these classifications, heavy smokers due to a developed tolerance to THC, showed little or no impairment in driving abilities, whereas habitual smokers revealed a doubled risk of accident fatality under acute influence of marijuana.

Does THC create worse impaired driving skills than alcohol?

In another study scientists measured blood alcohol levels and THC with its metabolite THC-COOH revealing that combination of cannabis and alcohol has a strong impact on probabilities of having an accident. At the same time, drivers with THC and its metabolites found in blood specimens, did not show significant increase in risk for accidents, on the other hand it has become evident that alcohol drastically doubles the risk compared to THC.


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