Blood-Brain Barrier and Pharmacokinetics

Soft Secrets
02 Nov 2012

While some people don't really care how Cannabis works - as long as it does - others are quite interested in the pharmacological action of the drug. By studying three scientific topics, it becomes a little easier to understand how the drug acts inside our bodies, as well as why we get high.

What is the blood-brain barrier?

The blood-brain barrier or BBB is just that: a central nervous system line of defense between the blood circulating through our bodies, and the BECF (brain extracellular fluid). The BBB is the main reason the human body can endure extreme injuries and infections, as not many substances are capable of passing through. The cerebrospinal fluid or CSF is protected by endothelial cells, which prevent microscopic intrusion from bacteria and other pathogens, as well as larger molecules.

These same cells allow the transfer of glucose, white blood cells and other helpful substances. In addition to prevention and protection, and occurring along all capillaries, the BBB cells are also capable of transporting substances (e.g., oxygen, hormones, carbon dioxide) across the barrier.

As too-large antibodies are incapable of crossing the barrier, the BBB is luckily able to prevent most bacterial or viral infections that might otherwise affect the brain. Unfortunately, however, if drugs are administered through the CSF, they are often unable to penetrate the BBB unless the barrier is inflamed – even antibiotics and cancer treatments.

What is unique about this barrier is that it does allow cannabinoids to penetrate and bind with the body's trans-membrane cannabinoid receptors, such as CB1 and CB2, mimicking the action of the neurotransmitter anandamide, an endocannabinoid produced within our bodies. Within about ten seconds of taking a toke, the plant's drugs cross the double-cell barrier and release a flood of wonderful feelings – which is why Cannabis has been the most widely-used illicit drug in human history and predates pharmacology.

While it may seem shocking that cannabinoids can penetrate a barrier that other substances cannot, this can explain the plant's efficacy at being an anti-inflammatory, analgesic and even a neuroprotective antioxidant. What is even more unusual is that certain animal studies have expressed the ease with which the metabolite of Δ-9-THC, known as 11-OH-Δ-9-THC, enters the brain – more easily than  Δ-9 in its original form.

This concentrated metabolite has a greater effect on the CNS due to its uptake in much higher quantities, possibly explaining why heavy smokers require four to eight weeks of sobriety before they feel entirely 'clean' again. In addition, there is evidence to support the theory that 11-OH-Δ-9-THC deposits in the liver after consumption and continues to impact the brain.

Pharmacokinetics and Cannabis

Although much research is dedicated to the effects of drugs on our bodies, much more attention is now being paid to the actions of our bodies upon the drugs. Effectively, pharmacokinetics is the study of the body's effect on drugs, testing aspects such as the mechanism and absorption of substances, rate of uptake and duration of effect, chemical changes or metabolic processes in the body relating to the substance, and excretion activity of the drug's metabolites by tracking enzyme action. This is important because of the long half-life that Cannabis displays inside the human body, as not only do the plant's drugs settle throughout certain human tissues and fat deposits, but the metabolized form of certain cannabinoids may continue to affect the user, or compound further drug use.

The pharmacokinetic process is known as ADME, with the latent addition of 'L'. A regards the absorption of the substance into the bloodstream; D refers to the dissemination (distribution) of the drug or compound throughout the body's fluids and tissues. The next step in the testing process is M for metabolism, also known as bio-transformation, as drugs are irreversibly changed into different substances. Finally, E regards the excretion of the substances which, when combined with metabolism, eliminates the substance from the body – this includes the observation that, in rare cases, some drugs never entirely exit our systems. The latter-day addition of an L for liberation accounts for how the drug is actually released from its formulation, which can lead to more effective prescriptions, more accurate dosage, etc.


Pharmacokinetic research reveals much about drugs that we cannot see: this scientific discipline often proves that, for example, different administration sites affect uptake rate, effectiveness and duration. Differing dosages of the same drug can have highly differing – and unusual – effects. These ideas have been represented anecdotally, especially in the Cannabis community, but through pharmacokinetics, scientists can actually prove these effects empirically. Now we know for certain that eating or drinking cannabinoid-infused products has a distinctly different effect on the body than smoking inhaled cannabinoids. Even so, vaporizing inhaled cannabinoids also presents a different action inside the body than smoking. With this information, the medical Cannabis community should be able to more effectively medicate its patients.


Conversely to pharmacokinetics, pharmacodynamics studies the effects of drugs on the body and both faculties are often studied in conjunction. This can be done in several ways: patient testimony and feedback, controlled pharmacological studies on humans, and animal testing. While it seems quite obvious that drugs affect us when they are consumed, it is important to understand exactly how they work and why they do what they do.

Opponents of Cannabis legalization look forward to negative results from clinical studies of the drug; however, even positive results can be manipulated or selectively reported to make a particular drug look more dangerous than it is. Likewise, pro-pot advocates have often been accused of focusing solely upon an abundance of non-empirical information to promote only the positive aspects of recreational and medical Cannabis use. Detractors tend to ignore the actual scientific research that proves cannabinoids can actually protect the body, from killing tumor cells to stimulating brain tissues. For this reason, it is especially important that both pharmacokinetic and pharmacodynamic research continues.

Soft Secrets