Opioids are substances which are derived from the opium poppy plant or its synthetic analogs, which act on the nervous system by reducing or eliminating the sensation of pain. Their ability to provide analgesia is the main reason they are used in the medical field. But these drugs (like morphine) have psychoactive properties and quickly generate dependency, even though their consumption had initially been subject to a medical prescription. This is precisely why opioid addiction with a medical prescription is a serious public health problem, which has already become an epidemic that is difficult to control. It has led to an increase in the number of illegal drugs dependent people as well as deaths from overdoses.
What Are Opioids?
An opioid is any endogenous or exogenous agent that binds to opioid receptors located primarily in the central nervous system and gastrointestinal tract. Although the term opiate is very often used to refer to all opium-like drugs, it is more appropriate to limit its scope to the natural alkaloids of opium and their semi-synthetic derivatives. There are three major classes of opiate substances:
- Opium Alkaloids– such as morphine (the prototype opiate) and codeine.
- Semi-synthetic Opioids– such as heroin and oxycodone
- Fully Synthetic Opioids– such as pethidine and methadone, which have a structure unrelated to the opium alkaloids.
The term opioid refers only to endogenous and exogenous substances with an affinity for these receptors, such as endorphins, enkephalins, or dynorphins. Opioids are frequently prescribed for their effective pain-relieving properties. There are three main classes of opioid receptors: μ, κ, and δ (mu, kappa, and delta), although more than seventeen have been described, including the receptors ε, ι, λ, and ζ (epsilon, iota, lambda, and zeta). In contrast, the σ (Sigma) receptors are not currently considered as opioids because their activation is not reserved for the reverse agonist of the opioid naloxone. They do not show an affinity for classical opioids and are stereoselective for dextro-rotatory isomers. Also, there are three subtypes of receptors μ: μ1 and μ2, and the recently discovered μ3. These are all receptors linked to Gi/o protein, which inhibit adenylate cyclase and decrease cAMP production. They also promote the opening of potassium channels and the closing of presynaptic calcium channels, all of which together decrease neuronal excitability.
Why is Opioid Addiction Generated?
Opioid analgesics are effective in the relief of chronic non-oncological pain. However, it generates tolerance, physical dependence, and risk of developing an opioid addiction in long-term treatment. These phenomena are caused by the agonist effect on the opioid receptors that modulate the pain pathways and produce an intense hedonic impact on the brain’s reward system. Repeated exposure to opioids produces neuro-adaptation that decreases the analgesic effect, produces anhedonia, the appearance of withdrawal symptoms, and behavioral changes that can trigger abuse and dependence. Current knowledge allows us to understand opioid dependence as a brain disease of multifactorial origin. In patients suffering from chronic pain, it has been established that the risk of developing an opioid addiction increases when there is a history of addictive behaviors and dependence, the presence of psycho-morbidity, a social environment conducive to consumption, and when doses above 120mg of morphine equivalent per day are prescribed.
On the other hand, an increase in the indiscriminate prescribing of these drugs has caused serious consequences in the general population in many countries, increasing the dependent population, opioid overdose mortality, and trafficking worldwide. Evidence-based clinical guidelines and expert consensus recommend that opioids should be part of multidisciplinary management, weighing the presence of risk factors and the expected benefit. Although it is difficult to demonstrate with evidence that these recommendations have an impact on reducing risk, they all emphasize prevention strategies, early research, and specific follow-up for the use of these drugs. The World Health Organization (WHO) continually communicates in its annual World Drug Report (WDR) its concern that increased access to opioid analgesics has not been balanced by safe prescribing. The world drug report concludes that increased availability and over-prescription, trafficking in synthetic opioids, and analogs from pharmaceutical and illegal production have fostered an overall epidemic increase in the prevalence of opioid abuse, dependence, and deaths. The most critical situations are in North America (the US and Canada), South East Asia, and Central Africa.
The effect these drugs have on the human brain are now known, especially those that modulate and affect the brain’s reward circuitry. We also know the bio-psycho-social factors that increase the vulnerability to develop a dependence on these substances and, particularly, in the patient (psycho morbidity, history of drug abuse). However, it remains a challenge to indicate a long-term opioid in safe conditions since, independent of individual factors, indiscriminate prescribing, lack of follow-up, and patient education, have caused serious opioid addiction problems in the general population as a result of the epidemic crisis of opioid abuse.