Modes of administration – evolutionary adaptive gaps

Modes of administration – evolutionary adaptive gaps

Humans are (so far) the most evolved species within the ecosystem of planet Earth, and the end result of a long evolutionary process going back to the primordial soup, out of which, as the dominant theory goes, all forms of life differentiated and evolved. It is increasingly apparent that the competition-driven Darwinian model is incomplete and that evolution is driven just as much by cooperative interaction as by competition, the yin and yang of evolution. Cooperation as a major force of evolution may have escaped evolutionists because of its ubiquity: for billions of years, life on our planet consisted of unicellular organisms that eventually congregated to form unicellular systems and then multicellular organisms. Interactive cooperation allowed the division of labor and the creation of specialized cells that eventually congregated in organs, allowing further specialization and differentiation, thus speeding up the evolutionary process. Just imagine survival of the fittest ruling the cells of your brain or your liver! Likewise, the major driving force of social systems, whether in the animal or human kingdom, is not competition, but interactive cooperation.

All life forms co-evolved interdependently in competitive symbiosis in which the vegetal kingdom plays a critical and distinctive role in the evolution of the animal kingdom. The vegetal kingdom provides directly or indirectly to the animal kingdom not only its food, but also its medicine, as well as substances that affect its mind, and may have been key to some critical evolutionary steps. This is indeed one of the great wonders and mysteries of life, and a powerful testimony to the prevalence of cooperation in the evolutionary process. The affinity between plants like poppy and cannabis and some of the most fundamental systems of brain activity, the dopaminergic and the cannabinoid system, both found in even the most primitive animal species, is nothing short of remarkable. Likewise, alcohol, as we will see in the chapter dedicated to that substance, is not only present in interstellar space, it was most likely one of the ingredients of the primordial soup theorized to be at the origin of life.

Humans co-evolved with psychoactive substances of natural origin in symbiosis with the vegetal kingdom. However, concentrates and extracts, such as distilled alcohol, heroin, cocaine, or amphetamines, or purely synthetic drugs, as well as direct routes of administration such as injection or inhalation, are novel features of our environment. As such, they create an evolutionary adaptive gap and are inherently pathogenic, although their use may be safe and warranted in some circumstances.[1]

Psychoactive substances can cross the blood-brain barriers and can be absorbed via various pathways. The digestive system, via the oral route, is the overly prevalent channel of administration of food and other substances in the animal kingdom, and is set up to withstand a wide variety of ingests. Furthermore, substances absorbed through the digestive system take a relatively long time to reach the brain as they are partly metabolized within the digestive system and the liver before they can reach the brain, which they do gradually. Therefore, ingestion is always the least dangerous and least addictive form of administration for a given substance.[2] The digestive administration process can be modulated to a certain extent. Thus, substances taken on an empty stomach reach the brain much faster than when they are taken with a meal.

The lungs, on the other hand, were designed to absorb air, and not much else. Even the smell of roses and other olfactory environmental signals are meant for the olfactory system located within the nose cavity, and not for the lungs. The lungs having a fractal structure, their total surface area is about the size of a tennis court, allowing fast and efficient oxygenation of the blood. Absorption through the lungs is extremely fast and powerful. Substances than can be absorbed through the lung tissue promptly reach the brain. Smoked heroin, cocaine or methamphetamine reach the brain within seconds of inhalation and peak within minutes. However, as we will see in a further chapter, cannabinoids and THC are different as they are strongly lipophilic. Their access to the brain is delayed upon inhalation, and the maximum “high” of cannabis is reached within 15 to 30 minutes.

As for veins, they were never designed to be punctured. Thus, it shouldn’t come as a surprise that intravenous injection is the fastest, most powerful and most damaging form of administration. Nasal absorption is notably slower than inhalation but still quite powerful and fast acting. Still, the nasal tissue is not meant to absorb anything more than infinitesimal doses of subtle and not so subtle aromatic substances ranging from utterly repulsive to sublime, from skunks to roses. Sublingual absorption is another fast track to the brain that is about on a par with nasal absorption. Chewing, such as chewing coca leaves or tobacco, involves a substantial amount of absorption through sublingual and other buccal mucosae.

Recreational drug users are motivated by the hedonistic reward provided by the substance. For most psychoactives except psychedelics, the intensity of the hedonistic reward depends in large part on the acuity of the peak intensity and the speed to reach this peak. A gradual rise of psychoactive concentration in the brain allows it to somewhat adapt to the substance and to modulate its effects to a certain extent, smoothing out its most damaging effects. A steep peak, on the other hand, doesn’t allow any adaptation; the more intense the peak, the more acute its effect. The most acute peaks create a surge of pleasurable sensation, the “rush” described by many injecting addicts, that they crave intensely. The steeper the peak, the more intense the rush, the more acute and disruptive will be the effects on the brain, causing a homeostatic imbalance which results in chronic dysregulation of the brain reward mechanisms and the brain’s neurotransmission in general.

Routes of administration that result in the rapid entry of a substance into the brain and/or faster rates of delivery have a greater effect on the neurotransmission systems in the brain, especially the reward systems, producing sensitization. Hard liquors are more damaging than beer or wine, especially on an empty stomach. Smoked opium reaches the brain faster and is more addictive than ingested opium. Injection and inhalation of active ingredients such as amphetamine, heroin or cocaine have the quickest entry and fastest rates of delivery. Therefore, they represent the most drastic evolutionary gap and have the most damaging effects.

Set and setting, expectation and intentionality affect the neuronal epigenetic environment. As such, they may influence the effects of particular substances. Thus, ritualistic use of tobacco where the plant is used with veneration and respect is vastly different from chain smoking of industrial cigarettes. Likewise, chronic pain sufferers under long-term opiate medication can usually discontinue without much problem once their medication is not needed anymore.[3] The absence of secondary reinforcers in the case of pain medication probably plays a critical role in preventing addiction. Nowhere is the set and setting more important than in the use of psychedelics.

[1] Randolph M. Nesse* and Kent C. Berridge, “Psychoactive Drug Use in Evolutionary Perspective,” Science 278, 63, 1997.

[2] Cannabis is somewhat an exception as ingested cannabis has stronger psychoactive effects than smoked cannabis (see Chapter 10).

A good video introduction to the endocannabinoid system

I highly recommend this short video Visualization of the endocannabinoid signaling system

Leanne does a great job at explaining how the endocannabinoid system operates as a retrograde signaling system. This is why cannabinoids act quite differently from other psychoactive substances. It may be why cannabinoids do not create physical dependance (as opiates or alcohol).



Drug Policy Reform World Brief

Drug policy reform in the making


Residents of Switzerland and the Basque Region of Spain can legally grow MJ for personal use since January 1st, 2012.

Denmark: The City Council of Copenhagen voted for legalizing marijuana. In the proposed scheme, cannabis products would be available in restricted quantities in government-run specialized stores. The government would also regulate production.

Poland: On December 9 the new Polish drug law came into effect and liberalized the drug policy. According to the new rules, the prosecutor will be able to dismiss the criminal charges if the offender possessed only small amount of drugs for personal use and he finds that punishment is not necessary.

Poles were asked about the idea of legalizing marijuana possession for personal use. On December 12th 2011, 67% of respondents answered yes, while only 32% said no – and about 1% of respondents were undecided. These results show that the public attitudes to drug policy liberalization are changing rapidly in Poland.

In the US:

Four states have asked federal officials to reclassify marijuana (Washington, Colorado, Vermont and Rhode Island.

MJ legalization initiative will be on the ballot in 2012 in Colorado, Washington, and probably California.

UK: The widely respected “The Lancet” published on January 6, 2012 a three-part Series of articles on drug use and addiction:

According to the Lancet, estimated 149—271 million people used an illicit drug worldwide in 2009. To give you a better idea, if drug users were a country, it would be the 5th largest country in the world.
Some of its key findings:

  • The international drug control system has not ensured adequate medical supply of opioids, particularly in low-income and middle-income countries, but also in some high-income countries.
  • The system has not effectively restricted the non-medical use of controlled drugs, and illicit drug production, manufacture, and use is now a global issue. Illicit drug use accounts for a substantial and increasing global burden of disease.
  • The system’s emphasis on criminalisation of drug use has contributed to the spread of HIV, increased imprisonment for minor offences, encouraged nation states to adopt punitive policies (including executions, extra-judicial killings, imprisonment as a form of treatment, and widespread violations of UN-recognised human rights of drug users), and impaired the collection of data on the extent of use and harm of illicit drugs, all of which have caused harm to drug users and their families.
  • The international system precludes policies that are more aligned to the risks of drug use and the adverse consequences of prohibition, such as the regulation of producers, consumers, and the conditions under which drugs are used.
  • Policy experimentation requires changes to the international treaties, which are possible in principle but unlikely in practice. Other options include renunciation of the treaties and re-accession with reservations, or adoption of a new treaty.

Bottom line on medical MJ

Bottom line on medical marijuana: prohibition is the worst possible form of control and create immense collateral damage. Medical marijuana has been a welcome relief — and a diversion, whose limits are sticking out more and more everyday. It also created a grey marketplace were some flourished.

All psychoactive substances, whether legal (alcohol, caffeine, tobacco, etc), prescription or illegal work the same way. Our neurons don’t read labels and couldn’t care less about legal status. Patterns of use are similar for all psychoactive substances: a small percentage will abuse while the vast majority use responsibly, and regular moderate use is often good for health (true for caffeine, alcohol, coca leaf, some prescription drugs, and probably MJ or opium). Moderate use of opium was the general rule for thousands of years as opium was one of the basis of medicine (and still is, ironically – opiates still are the best pain-management tools around).

The war on drugs is also a cultural war, touting alcohol, the dominant psychoactive  substance of Western civilization, against the dominant psychoactive substances of Andean or Eastern civilization: coca leaf, cannabis and opium; meanwhile, the western-dominated pharmaceutical industry is flooding the planet with a new generation of psychoactive substances in its (so far very successful) attempt at medicalization of normalcy. This, by the way, is one of the dominant theme of my just released ” World War-D: the case against prohibitionism. A roadmap to controlled re-legalization.”

The only viable long-term solution to the drug issue: global re-legalization under a multi-tiers “legalize, tax, control, prevent, treat and educate” regime with practical and efficient mechanisms to manage and minimize societal costs.

Far from giving up and far from an endorsement, controlled legalization would be finally growing up; being realistic instead of being in denial; being in control instead of leaving control to the underworld. It would abolish the current regime of socialization of costs and privatization of profits to criminal enterprises, depriving them of their main source of income and making our world a safer place.