11-Hydroxy Delta-9 THC

11-Hydroxy Delta-9 THC is a metabolite of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. 

When THC is ingested, it undergoes metabolism in the liver, where it is converted into 11-Hydroxy Delta-9 THC by the enzyme cytochrome P450 3A4. 

This metabolite is known for its potent psychoactive effects and plays a crucial role in the overall pharmacokinetics of THC.

What is 11-Hydroxy Delta-9 THC?

Definition and Chemical Structure  [7.] 

11-Hydroxy delta-9 THC is a phytocannabinoid and a metabolite of delta-9 THC.  The 11-hydroxy metabolite is characterized by a key structural difference: it is Delta(9)-tetrahydrocannabinol in which the methyl group at C-11 has been hydroxylated.

This slight structural alteration significantly changes the compound's pharmacological properties. Unlike delta-9 THC, which is known for its psychoactive effects, 11-hydroxy delta-9 THC exhibits enhanced potency due to this modification. 

Its chemical structure is crucial for understanding its interactions within the body, particularly with the endocannabinoid system, and its role in various physiological processes.

Metabolic Pathway: From Delta-9 THC to 11-Hydroxy Delta-9 THC  [4.]

The transformation of delta-9 THC to 11-hydroxy delta-9 THC is primarily a liver-mediated process. 

Human liver enzymes catalyze the transformation of THC to 11-OH-Δ-9-THC, which is then further processed to its glucuronide form. This metabolic pathway is crucial for making THC water-soluble, facilitating its excretion. 

When administered intravenously to humans, 11-Hydroxy-Δ9-tetrahydrocannabinol induces psychological and pharmacological effects that last for several hours. The compound and its metabolites are expelled through urine and feces over a period exceeding one week.  [6.] 

Continuing research not only enhances understanding of THC metabolism but also provides a foundation for developing reference standards for THC and its metabolites, crucial for drug testing and therapeutic monitoring.

Physiological Effects and Comparison with Delta-9 THC

11-Hydroxy delta-9 THC is known for its potent psychoactive effects, which are often considered more intense than those of delta-9 THC.  [5.] 

Δ9-Tetrahydrocannabinol (THC) and its psychoactive metabolite, 11-hydroxy-THC (11-OH-THC), are frequently detected in toxicology tests following vehicular accidents and assessments of driving under the influence.  [5.] 

One study examined 18 long-term heavy cannabis users during a seven-day monitored abstinence period, analyzing plasma concentrations of THC, 11-OH-THC, and the inactive metabolite 11-nor-9-carboxy-THC (THCCOOH). The presence of THC in plasma after such a prolonged abstinence period highlights its potential to cause lingering neurocognitive impairments in chronic users.  [5.] 

This heightened potency is largely attributed to its increased ability to cross the blood-brain barrier, resulting in pronounced cognitive and perceptual effects.  [3.]  The differences between these two compounds are vital in both clinical and legal contexts, especially in understanding the implications of cannabis use, dosing in therapeutic settings, and assessments of impairment or intoxication.

11-Hydroxy Delta-9 THC as a Biomarker

The investigation into 11-hydroxy delta-9 THC as a biomarker reveals its crucial role in various clinical, pharmacological, and legal contexts. 

Clinical Implications

11-Hydroxy delta-9 THC serves as a vital biomarker in clinical settings, particularly in understanding the pharmacokinetics of THC. Its presence and concentration in the body can provide insights into how an individual metabolizes cannabis, which is essential for dosing accuracy in therapeutic applications. 

In drug abuse monitoring, the detection of THC metabolites may persist after use.  Despite methodological limitations such as incomplete hydrolysis of cannabinoid conjugates and instability of glucuronides under storage, one study reveals persistent elevation of cannabinoid levels.  [8.] 

After 19.5 hours of monitored abstinence plasma THC was detectable, indicating prolonged excretion which challenges the assumption that detectable THC always signifies recent cannabis use. 

This is particularly relevant for frequent users, where tissue accumulation and slow release into the blood may extend detection times. The study demonstrates that THC, unlike its metabolites, does not accumulate significantly, possibly due to rapid gastrointestinal metabolism.   [8.] 

Therapeutic Potential  [1.] 

The therapeutic implications of 11-hydroxy delta-9 THC monitoring may help to understand the efficacy of cannabis-based treatments for various conditions. By monitoring levels of this metabolite, healthcare providers can optimize treatment regimens for conditions such as chronic pain, anxiety, and certain neurological disorders. 

Its potent psychoactive effects also necessitate careful monitoring to balance therapeutic benefits with potential side effects. Understanding the pharmacological profile of 11-hydroxy delta-9 THC is key to harnessing its therapeutic potential while mitigating risks.

Testing for 11-hydroxy delta-9 THC in meconium is also useful for confirming prenatal exposure to marijuana, reflecting its importance in both clinical and forensic settings.  [9.] 

Legal and Ethical Considerations

In legal contexts, 11-hydroxy delta-9 THC is a significant biomarker for determining cannabis impairment. Its heightened psychoactive properties, compared to delta-9 THC, make it an indicator of relatively recent cannabis use and potential intoxication, although questions have been raised about the duration of validity of the presence of this biomarker.  [8.] 

Ethically, the detection of this metabolite raises questions about privacy, consent, and the use of cannabis-related data in legal and employment settings. Navigating these considerations requires a nuanced understanding of the societal implications of testing for metabolites of marijuana.

Laboratory Testing for 11-Hydroxy Delta-9 THC

Laboratory Test Information and Sampling Methods

Common samples to test for the presence or 11-hydroxy Delta-9 THC include blood, urine, and sometimes meconium, saliva or hair.  

Blood tests are often considered the most direct method for measuring active substances, including 11-hydroxy delta-9 THC, while urine tests are typically used for detecting past usage due to the presence of metabolites. 

The selection of the sample type is influenced by the testing purpose, such as clinical diagnosis, therapeutic monitoring, or legal investigation.

Interpreting Test Results

Generally, the presence of 11-hydroxy delta-9 THC in the body is evidence of recent marijuana use.  The testing objectives become essential in interpreting an individual’s test results.  

In the case of medical or therapeutic assessment, testing the levels of marijuana metabolites such as 11-hydroxy delta-9 THC should be understood in the clinical context of the patient.  Symptom assessment and amelioration of complaints must be taken into account alongside screening tests.  

In the current cultural setting wherein marijuana use is increasingly legalized, establishing parameters for safe use is essential, particularly in the case of driving.  As an example, the state of Washington established I-502 which set a per se level of 5ng/mL of active delta-9-tetrahydrocannabinol (Δ9-THC) in blood for cannabis-impaired driving.  [2.] 

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