Opioids
An opioid is any psychoactive chemical that resembles morphine or other opiates in its pharmacological effects. Opioids work by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract. The receptors in these organ systems mediate both the beneficial effects and the side effects of opioids.
Although the term opiate is often used as a synonym for opioid, the term opiate is properly limited to the natural alkaloids found in the resin of the opium poppy (Papaver somniferum), while opioid refers to both opiates and synthetic substances, as well as to opioid peptides.
Opioids are among the world's oldest known drugs; the therapeutic use of the opium poppy predates recorded history. The analgesic (painkiller) effects of opioids are due to decreased perception of pain and a decreased reaction to pain as well as increased pain tolerance. The side effects of opioids include sedation, respiratory depression, constipation, and a strong sense of euphoria. Opioids can cause cough suppression, which can be both an indication for opioid administration or an unintended side effect. Opioid dependence can develop with ongoing administration, leading to a withdrawal syndrome with abrupt discontinuation. Opioids are not only well known for their addictive properties, but also for their ability to produce a feeling of euphoria, motivating some to use opioids recreationally.
Chemistry
Opioids are based upon morphine and opium-like structures. They work via their similar chemical structures to the endogenous opioids in the body. The morphine-based opioids generally contain a benzene ring attached to two partially unsaturated cyclohexane rings, known as the phenanthrene group.
Mechanism of Action
Opioids act on the three main classes of opioid receptor in the nervous system, μ, κ, δ (mu, kappa, and delta). Each opioid is measured by its agonistic or antagonistic effects towards the receptors, with the responses to the different receptor sub-types (e.g. μ1 and μ2) providing even more effects.
Subjective effects
Physical effects
- Pain relief - This component is subjectively different from other anaesthetics as it does not necessarily remove the pain entirely whilst still remaining equal in terms of its effectiveness. Instead of directly suppressing pain these substances simply dull the perceived sensation and cover it up with feelings of physical and emotional pleasure.
- Euphoria
- Itchiness
- Constipation
- Respiratory depression - At low to moderate doses, this effect results in the sensation that the breath is slowed down mildly to moderately, but does not cause noticeable impairment. At high doses and overdoses, opioid-induced respiratory depression can result in a shortness of breath, abnormal breathing patterns, semi-consciousness, or unconsciousness. Severe overdoses can result in a coma or death without immediate medical attention.
- Cough suppression
- Metabolic depression
- Difficulty urinating
- Nausea
- Stomach cramps
- Sedation
- Pupil constriction (pinning)
Cognitive effects
- Euphoria - By both u agonism and downstream dopamine reinforcement
- Increased motivation - Some opioids (such as kratom are more stimulating than others and seem to enhance motivation
- Suppression of anxiety
Visual effects
- Internal hallucinations - State of semi-consciousness during nodding stage
Pharmacological Classes
Naturally occurring
Opiates are the class of naturally forming opioid agonist alkaloids, which are found within the latex of the Opium Poppy (Papaver Somniferum), and in smaller quantities within other species of poppy.
- Morphine
- Codeine
- Thebaine (Not recreational, used as precursor for semi-synthetic opioids)
- Other alkaloids contribute to the effects of poppy pod/seed tea and other preparations of the raw latex
Semi-synthetic
Opioids refers to both semi-synthetic and fully-synthetic opioid agonists. Natural opioid agonists can be converted by chemical syntheses to a variety of substances, which have differing duration and potency.
- Diacetylmorphine (Heroin)
- Dihydrocodeine
- Hydrocodone
- Hydromorphone
- Oxycodone
- Oxymorphone
- Buprenorphine (Subutex)
- Naloxone (Narcan; powerful antagonist, precipitates instant withdrawal and is used to recover from overdose)
Synthetic
Synthetic opioids do not contain the classic morphinan backbone, as they are not derived from alkaloids of the poppy plant.
Other sources
- Kratom contains mitragynine alkaloids which are responsible for the μ-opioid receptor agonism of kratom leaf, its extracts and other preparations.
Toxicity and Harm Potential
When used in safe dosages, in terms of physical and neurological toxicity most opiods are remarkably safe with the long term effects generally only consisting of constipation. The negative aspects associated with opioids do not stem from toxicity but psychological addiction and dependence.
Tolerance and addiction potential
Due to the overwhelmingly euphoric nature of these substances, the recreational use and abuse of opioids has an extremely high rate of addiction and dependence. This is combined with a tolerance which builds up quickly, necessitating that the user take increasingly high dosages in order to get the same effects.
Discontinuation
Post abuse withdrawal symptoms (PAWS) are commonly reported following abuse of opioids over a period of several days. PAWS are not expected to occur in opioid-naive individuals or those who use infrequently, as it is caused by the downregulation of opioid receptors in response to repeated administration.
Onset and duration
The perceived effects of PAWS differs between individuals and for each opioid. The onset and duration are intrinsically linked to the substance's clearance half-life, μ-opioid receptor affinity, and the individual's current level of tolerance.
Symptoms
PAWS covers a broad range of symptoms. Most commonly the user will experience flu-like effects such as congestion and sneezing, rebound sensitivity to pain and tactile stimulation, restless leg syndrome, insomnia and diarrhea.
Opioids with a short half-life, such as diacetylmorphine (Heroin) are well known to induce withdrawal symptoms in tolerant individuals within several hours of having cleared the body. Longer eliminating opioids like methadone will exhibit symptoms of withdrawal much later, but the effects will linger far in excess of shorter acting opioids as the body will take longer to reach homeostasis.
Mitigation
PAWS can be mitigated by slowly tapering the dosage over a period of days, which will let receptors recover somewhat before discontinuation. This will lessen severity of symptoms but likely prolong their duration. Switching to a weaker opioid such as codeine or even Kratom can lessen the perceived symptoms but is likely to also prolong the period of withdrawal. Switching to a shorter acting opioid like diacetylmorphine (Heroin) prior to discontinuation will shorten the duration of symptoms when coming from a longer eliminating opioid such as methadone.
Alternatively, the specific opioid in use can be substituted with less euphoric opioids such as buprenorphine; or high doses of the anti-diarrhea medication loperamide (Imodium), which does not cross the blood/brain barrier due to endogenous uptake inhibition caused by p-Glycoprotein, but provides relief of homeostatic symptoms by agonism of peripheral opioid receptors.
Precipitated withdrawal
Some combinations of drugs are known to induce the state of withdrawal by blocking the receptors. Naloxone (Narcan), which can be administered to recover from an opioid overdose, has a higher affinity to μ-opioid receptors than most opioids so knocks off any agonists then blocks the binding site until eliminated from the body. Multiple doses of naloxone may be required as overdose can reoccur if the original opioid has a longer elimination half life (note, there are exceptions, like that one particular opioid which covalently bonds to the receptor site).
Buprenorphine (Subutex), often used in addiction therapy or as prescribed, also has a higher affinity than many other opioids and will cause precipitated withdrawal symptoms if another type of opioid is coadministered before it has been eliminated.