Cannabinoids, those green objects of desire

A short reflection, by the doctor (and writer) Ricardo Tronconi, whose discipline is palliative medicine, on the risks and virtues of the use of cannabinoids for therapeutic purposes, permitted in Italy since 2006, but still largely opposed or viewed with suspicion. The author wished to speak in person on this delicate subject, an important point in several of his short stories, such as ‘Aniel Day‘ and ‘La Pentagonia semicircula‘.

Is a person taking cannabinoids an addict?

Although cannabinoid-based magistral preparations have long been available in Italy in pharmacies with ad hoc laboratories, their prescriptions by doctors are still limited in number, despite the fact that studies on the effects of cannabis show new knowledge of the therapeutic potential of the molecules found in the plant’s inflorescence. The reasons for this apparent lack of interest in the herbal drug are probably to be found in the considerable number of doctors who are still unfamiliar with the subject. Another reason lies in the cultural qualms infused with prejudice towards a substance known mainly for its voluptuary use. It is precisely the latter that is the hotbed of ideas that make a patient who takes cannabis an addict. If this were really the case, we would have to consider everyone who drinks wine an alcoholic. A further brake on the use of cannabis in therapy is the fear of inducing addiction.

Complex addiction

Let us therefore shed some light on this, as addiction is a subject about which patients always want to be reassured. The prescribing doctor is mainly interested in dividing addiction into two broad forms: simple and complex. The latter is characterised by being of exclusive concern to the ethylist, the gambling addict, the drug addict, the hypersexual (to name but a few).

In complex addiction, the substance or object of addiction takes a central role in the individual’s life and compromises his or her physical and psychological health. By contrast, none of this happens in simple addiction, which develops in the course of an analgesic therapy. In the latter, in fact, what counts is the effectiveness of the substance taken to combat the pain. If I have severe pain that I can neutralise with cannabis, I will become dependent on the drug until the symptom wears off. However, I will not remain dependent on it once the therapy has ended.

Simple addiction

Simple addiction does not only concern opiods, cannabinoids or psychoactive drugs, but also products that have nothing to do with the latter. An example: heartburn controlled by a prazole (a protector of the gastric mucosa) will lead us towards simple dependence on a drug that is certainly not psychoactive. That said, the practising physician is undoubtedly interested that simple dependence does not turn into complex dependence. The data available to date on pain therapy with morphine and cannabis show that in the vast majority of cases complex dependence does not develop in relation to these drugs. Therefore, not prescribing opioids and cannabinoids for fear of developing complex dependence has no reason to be. However, it remains essential to maintain contact with the patient throughout the duration of therapy. We must not to leave him/her alone in the management of his/her discomfort.

All studies on the subject

In recent years, studies on cannabis have followed one another at a relentless pace and PubMed.gov cites more than forty thousand articles to date involving the best-known components of the plant’s inflorescence. The latter are tetrahydrocannabinol (THC) and cannabidiol (CBD), but only the former is psychoactive and is the reference molecule for the volutary use of the inflorescence. In medical therapy, both components play an important role, as do all the other molecules present in the plant. Indeed, the use of individual components (THC or CBD) does not provide the same therapeutic benefits as the inflorescence used in its entirety. From this it can be deduced that, in addition to cannabinoids, other components (terpenes, flavonoids) are also essential in order to achieve the maximum effect of the phytopharmaceutical.

How cannabinoids work

With regard to pharmacodynamics (mechanism of action), what we know today mainly concerns two receptors through which certain cannabinoids (THC and CBD) are said to exert their action. These receptors belong to the so-called endocannabinoid system, which we possess as we ourselves produce cannabinoid-like molecules. The first endocannabinoid to be isolated belongs to a new class of neuro-modulators that mimic the effects of psychoactive compounds found in cannabis. It is called anandamide, from the Sanskrit word ananda, meaning bliss. The two receptors of the endocannabinoid system currently known are CB1 and CB2. CB1 is found predominantly, but not exclusively, in the central nervous system. CB2 is found predominantly, but not exclusively, at the level of the immune system. What we know today of the action of cannabinoids through CB1 and CB2 receptors does not explain the complexity of the mechanisms that develop from the intake of cannabis. We therefore hypothesise that not only cannabinoids, but also other components of the inflorescence, are able to activate enzymatic systems or membrane ion channels by not binding to known receptors.

THC and CBD

To date, we know that THC has an affinity for the CB1 receptor and also has intrinsic activity towards it, i.e. it activates it. By contrast, CBD only has an affinity for the same receptor, but does not activate it. It would therefore seem a contradiction to administer THC and CBD together, as the latter would block the receptor on which THC acts. In reality, this is not the case and it is hypothesised that the end result is a combination of these actions with CBD not antagonising, but modulating the action of THC. Ultimately, CBD would control the action of THC by complementing it and lengthening its time. Further studies will be needed to investigate the complex mechanisms that are activated when cannabis is taken.

In nature, cannabinoids are found in an acidic state and are inactive. To activate them, decarboxylation is required, which is achieved by heating the inflorescence. The temperatures reached for decarboxylation are crucial to obtaining an optimal product, free of toxic substances that would pollute its preparation.

How cannabinoids are used in pain therapy

In pain therapy, the intake of cannabinoids requires the preparation by the pharmacist of sachets to be used in the preparation of decoctions, and oleolites by the sublingual route. In cases where immediate absorption of the various components is required, vaporisers may be used. These bring the inflorescence to the desired temperature by vaporising it to be inhaled by the patient. The main use of cannabinoids in medical therapy relates to chronic pain that does not respond to conventional painkillers. Cannabis can be used in combination with other drugs or as monotherapy as the sole pain-relieving drug. For instance, it may also be prescribed as an appetite stimulant in anorexia nervosa, in nausea and vomiting from chemotherapy. Other applications are in Gilles de la Tourette syndrome for reduction of involuntary movements, in glaucoma for its hypotensive effect. Further studies are in progress to evaluate its use in other diseases.