Pharmacology
DrugBankDescription
Opium is the first substance of the diverse group of the opiates. It has been known for a long time, and the first evidence of a poppy culture dates from 5 thousand years by the Sumerians. During the years, opium was used as a sedative and hypnotic, but it was determined to be addictive. Opium is extracted from _Papaver somniferum_, which is more known as poppies. This plant is an integrant of the Papaveraceae family, and it is characterized by solitary leaves and capsulated fruits. Therefore, opium is a sticky brown resin obtained by collecting and drying the latex that exudes from the poppy pods. Once extracted, opium contains two main groups of alkaloids; the psychoactive constituents which are in the category of phenanthrenes and alkaloids that have no central nervous system effect in the category of isoquinolines. Morphine is the most prevalent and principal alkaloid in opium, and it is responsible for most of the harmful effects of opium. Opium has gradually been superseded by a variety of synthetic opioids and general anesthetics. Some of the isolated derivatives of opium are morphine, noscapine, strychnine, veratrine, colchicine, codeine, and quinine. Opium is a prohibited drug of abuse in most countries, but the illegal production of this drug and its derivatives keeps being registered. There is some legal production of opium in different countries for the obtention of alkaloids by extraction.
Mechanism of Action
Opium produces its effects by activating specific G protein-coupled receptors in the brain, spinal cord, and peripheral nervous system. There are three major classes of opioid receptors being δ-opioid, κ-opioid and μ-opioid. Opium will generate an agonist activity which will later open the potassium channels and prevent the opening of voltage-gated calcium channels. This activity causes a reduction in neuronal excitability and inhibits the release of pain neurotransmitters. The addictive character of opium is related to the binding to the μ-opioid receptors, which will activate dopaminergic neurons in the ventral tegmental area of the midbrain and thus, enhance the dopamine release in the nucleus accumbens. This mechanism involves the reward activity of the mesolimbic dopaminergic pathway.
Pharmacodynamics
Opioids can reduce the intensity and unpleasant feeling of pain. The unspecific effect of opium to the different opioid receptors produce the generation of various effects such as sedation, euphoria, dysphoria, respiratory depression, constipation, pruritus, nausea, and vomiting. It is reported that the secondary effects tend to be diminished as long-term use tolerance is developed. Some reports have also shown an opioid-driven impairment of the hypothalamic function that can result in a loss of libido, impotence, and infertility. Patients have reported a sensation of stress relief even in presence of pain as well as the presence of sedation, hypoventilation, cough inhibition, prolonged apnea, myosis and respiratory obstruction. In the cardiovascular system, there are reports of peripheral vasodilatation, including cutaneous causing flushing of the face, neck, and thorax, impaired sympathetic reflexes and postural hypotension. In the gastrointestinal and urogenital system, the increase in smooth muscle tone has been shown to produce reduced peristalsis, delayed gastric emptying and urinary retention.
Metabolism
Opium contains 50 different alkaloid opiates. The most common metabolism of opiates is to be ultimately converted to morphine which is further converted to morphine-3,6-diglucuronide. Opioids are metabolized vastly by the enzyme CYP 2D6 and any mutation in this kind of enzyme or coadministration with drugs that interfere with this enzyme may generate a change in the metabolism speed. For years, because of this metabolism pathway, it was very hard to differentiate between illicit heroin users and involuntary exposure to poppy seeds. The original tests for this differentiations were based in the presence of morphine in urine without evidence of 6-monoacetylmorphine. Now it is known the presence of a glucuronide metabolite only in the consumption of heroin called ATM4G and this allows a clear differentiation of the consumption of illegal heroin and poppy seed ingestion.
Absorption
After oral administration, opium bioavailability is poor. In the form of opioid tincture, the Cmax and AUC of opium are between 16-24 mg/ml and 3237-6727 ng/ml.h, respectively.
Indication
Opium and its derivatives are the most commonly used medications for the treatment of acute and chronic pain. Opium and its alkaloid-derivatives can also be used as tranquilizers, antitussives and in the treatment of diarrhea. The direct use of opium is not common nowadays but the use of some of its derivatives such as morphine and codeine, as well as the use of a tincture of opium for severe diarrhea can be seen in medical practice. Illegal use of opium has been registered to be for both recreational and medicinal purposes.
Half-life
The half-life of opium ranges between 3-10 hours.
Protein Binding
The protein binding of the alkaloids that form opium, such as morphine and codeine, can range from 20-60% depending on the specific alkaloid. The highest binding proteins for opium alkaloids are albumin and beta-globulin II.
Elimination
Opium is a mixture of different alkaloids including morphine and codeine. After a single ingestion of opium preparations, codeine and morphine can be found excreted in urine. The presence of codeine and morphine in urine seems to be detectable 2-12 hours and 2-36 hours post administration, respectively. The urinary excretion of morphine and codeine seems to be longer as the dose of opium is increased. After multiple dosages of opium, the presence of codeine and morphine in urine could be detected even after 48 and 84 hours post administration, respectively. After ingestion of poppy seeds, it is possible to collect morphine and codeine in urine 3-25 hours and 3-22 hours after administration, respectively.
Volume of Distribution
Opium presents a large volume of distribution that exceeds the total body water.
Toxicity
DrugBankToxicity (DrugBank)
Some toxicity concerns from the consumption of opium are the generation of addiction, physical dependence and tolerance to the effect. Studies regarding the opioid tolerance in the treatment of chronic pain have not been systematically investigated. There are also concerns about the opioid-driven modification of endocrine function, currently reported as lower testosterone levels, loss of libido, amenorrhea and infertility.
Effect Profile
Curated + 164 ReportsStrong euphoria with strong itching/nausea, moderate sedation, mild pain relief
Tolerance & Pharmacokinetics
drugs.wikiNo tolerance chart. Our decay curves for opioids were estimates, and a curve can make tolerance look longer-lasting than it is, which is the dangerous direction.
Opioid tolerance drops fast when you stop, and even a few days off can be enough, so a dose that used to be normal can now stop your breathing. Overdose deaths rise sharply after prison, detox or leaving treatment, and tolerance also falls during a hospital stay. After any break, start with a much smaller amount, try a test dose first, don't use alone, and keep naloxone within reach. Alcohol, benzodiazepines, gabapentinoids and other sedatives make an opioid overdose much more likely.
Sources: FRANK: heroin · National Harm Reduction Coalition · WHO: opioid overdose · Merrall et al. 2010 · Binswanger et al. 2007 · Strang et al. 2003 · FDA 2019: gabapentinoids and breathing
Demographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
Erowid + BluelightEffects aggregated from 137 experience reports (87 single-substance Erowid + 77 Bluelight)
Effect Sentiment Distribution
Confidence Distribution
Each bar is the share of reports mentioning the effect; its whisker, and the band on the rows below, is the 95% interval: where the share could plausibly be with other reports of the same kind.
Positive Effects 64
Adverse Effects 39
Show 19 more adverse effects
Show 22 neutral or unclassified mentions
Also reported in combinations. In the 60 Opium reports where another drug was taken too, 6 (10.0%) mention hospital, emergency services or an overdose, 0 (0.0%) a seizure and 3 (5.0%) psychosis. In the 87 single-substance reports: 16.1%, 0.0% and 0.0%. These are not in the figures above: they cannot be put down to Opium alone, and a mention is not always something that happened to the writer.
Dose-Response Correlation
How effect frequency changes across dose levels. Whiskers, and the numbers' hover text, give each figure's 95% interval.
Not drawn, too few reports (a dose tier needs 20): Oral Common (n=10). Why 20?
Dosage Distribution
Dose distribution from experience reports, one dose per report (the first listed). Doses above Q3 + 3×IQR, far above what people typically take, are left out of the median and range and listed under each route: most are real heavy doses or overdoses, not mistakes.
Real-World Dose Distribution
ErowidFrom 30 of 141 recorded dose entries: those that state a weight (mg, g or µg), in routes with at least five of them. Values above Q3 + 3×IQR, far above what people typically take, are left out; they can include real heavy doses and overdoses, not only mistakes.
Oral (n=18)
Smoked (n=12)
Common Combinations
Most co-occurring substances, as a share of all 147 reports filed under Opium; whiskers are 95% intervals
Form / Preparation
Most common forms and preparations, as a share of the 103 reports that give one; whiskers are 95% intervals
Body-Weight Dosing
Dose per kg of body weight, one dose per report (the first listed), from reports giving a weight of 30–250 kg. Doses above Q3 + 3×IQR, far above what people typically take, are left out of the median and range and listed under each route.
Oral
Smoked
Redose Patterns
Redosing behavior across 115 reports