Igor Domsac & Sarah Russo | June 28, 2024
Papaver somniferum, commonly known as the opium poppy, is an annual herbaceous plant in the Papaveraceae family cultivated for its medicinal alkaloids, edible seeds, and oil. The plant is characterized by its lobed leaves and vibrant flowers, which range from white to deep purple. The poppy plant has several distinct parts. The seed capsule contains numerous tiny seeds which are widely incorporated in culinary contexts and found in supermarkets for baking and cooking. [1] Poppy seeds are valued for their nutty flavor and nutritional content. The plant’s flowers are also cultivated for ornamental purposes and are popular due to their striking appearance.
The latex of the plant, which is the source of opium, is extracted from unripe seed capsules through incisions that allow for the collection of sap. This latex contains various alkaloids with medicinal properties. Beyond its medicinal applications, the opium poppy serves multiple purposes. [2] It is important to differentiate between the opium poppy’s resin and other applications. While the resin (latex) has potent alkaloids, the seeds and ornamental flowers do not contain these alkaloids and are safe in everyday contexts. All plants in the Papaver genus have opium alkaloids, but Papaver somniferum is the most potent and commercially significant. [3]
Origin/History
Papaver somniferum has been cultivated since the Neolithic era, more than 5,000 years ago. It played a significant role in ancient civilizations such as Sumer, Egypt, and Greece as part of medicine and ritual work. Until the invention of modern pharmacology, humanity had very few means to combat something as terrible and paralyzing as pain. In this context, a plant capable of alleviating pain—a rare and invaluable gift—became an immeasurable blessing. In these cultures, the plant’s latex was processed to produce opium, which was employed for pain relief and sedation. [4] The seeds and other parts of the plant were also incorporated into various ceremonial rituals, symbolizing sleep, death, and rebirth. [5] The poppy’s potent properties made it a revered element in both healing traditions and spiritual observances. [6]
Opium poppy is a dream herb, inducing vivid imagery for those in subconscious states. One of its active ingredients, morphine, is related to the Greek god Morpheus, the god of dreams. [7] Friedrich Sertürner, who first isolated morphine from the opium poppy in 1803, chose this name because of the compound’s profound sedative and dream-inducing properties. [8]
The cultivation and trade of opium poppies have influenced cultures and economies for millennia. The trade of opium along the Silk Road facilitated economic growth and cultural exchanges between East and West, enhancing cross-cultural interactions. [9,10] During the colonial era, the British expanded opium cultivation in India to supply China, a policy that had profound economic repercussions and contributed to the Opium Wars. [11]
Ancient Beginnings
Archaeological evidence suggests that Papaver somniferum was cultivated in Europe as early as 5,000 BCE. [12] The Sumerians, one of the earliest civilizations, referred to the opium poppy as Hul Gil, meaning the “joy plant.” They primarily consumed opium orally, preparing it as a potion or mix it with other substances to treat various ailments such as pain and insomnia. [13] Opium poppy spread from the Sumerians to the Assyrians, Babylonians, and Egyptians primarily through extensive trade networks and cultural exchanges in the ancient Near East. [14] The Assyrians and Babylonians used opium both by inhalation and orally. It was common to burn opium and inhale the fumes. Additionally, they ingested it in the form of concoctions or mixed with other medicinal ingredients. [15]
In Egypt, opium poppy held a place of importance both medicinally and ritually. It was documented in the Ebers Papyrus, an ancient medical text dating back to around 1,550 BCE, describing the analgesic and sedating properties of the plant. [16] It was often ingested in the form of a drink or mixed into food. Additionally, opium was sometimes applied topically as part of medicinal poultices to treat wounds and other conditions. [17] It was also depicted in Egyptian art and hieroglyphs, highlighting its significant role in their society. [18] The plant is known to be one of the world’s first antidepressants, [19] recognized for its ability to positively impact mood and mental health. [20]
Greco-Roman Influence
Through ancient trade routes, the knowledge of Papaver somniferum spread to the Greeks and Romans, who integrated it into their medical practices. Hippocrates, often considered the father of medicine, mentioned the analgesic properties of the opium poppy as early as the 5th century BCE. [21] The Greek physician Dioscorides described the various therapeutic attributes of the opium plant and its preparations in his seminal work De Materia Medica. The Romans continued this tradition when the prominent physician Galen also recognized and documented the medicinal properties of opium. [22]
The Spread to Asia
Scholars and physicians expanded on the growing knowledge of Papaver somniferum during the Islamic Golden Age. Avicenna, a Persian polymath, included opium in his medical writings by noting its analgesic and hypnotic effects. [23] Through trade and colonization, the knowledge and cultivation of opium spread to China and India. By the 7th century, the Chinese were cultivating opium poppies and processing its latex for medicinal purposes. [24] In India, opium became deeply integrated into traditional Ayurvedic medicine. [25]
Opium use was integrated into daily life, often consumed in grape syrups or mixed with other substances like hashish. Its use was considered a means of preserving physical and mental health, with long-term users reportedly immune to ailments like colds and flu, which are particularly debilitating for the elderly. [26]
Medieval to the early modern period
In medieval Europe, opium was reintroduced during the Crusades. Those who returned brought back knowledge of the plant’s attributes from the Middle East. [27] It became a common remedy in apothecaries across Europe. By the 16th and 17th centuries, European colonizers and traders spread opium to new regions, including Southeast Asia. This spread was not merely through exploration but also via establishing colonial dominance, which imposed European economic and cultural practices on these regions. [28] The commodification and trade of opium by European powers often led to significant social and economic disruption in the colonized areas. It deeply embedded opium in global trade networks and contributed to various local and regional conflicts. [29]
The Opium Wars
The 18th and 19th centuries marked a dark period in the history of Papaver somniferum, with the British East India Company cultivating opium in India and exporting it to China. The primary motive for this trade was economic: Britain faced a significant trade imbalance due to its high demand for Chinese tea, silk, and porcelain, which were paid for in silver. To mitigate the outflow of silver, the British decided to trade Indian opium for Chinese goods. This led to widespread substance use disorder in the region and resulted in the Opium Wars (1839-1842 and 1856-1860) between China and Britain. [30]
Before British intervention, opium was used medicinally in China, but its recreational use was relatively limited. However, as British opium imports increased, recreational use surged, leading to widespread addiction. Opium dens became prevalent, serving as social hubs where people gathered to smoke and socialize. [31] An opium den was a place where opium was sold and smoked, prevalent in the 19th century across regions such as China, Southeast Asia, North America, Britain, and France. [32,33] The conflicts forced China to cede territory and grant trade concessions to Britain, profoundly impacting Chinese society and politics. [34]
The opium trade severely impacted China’s economy, draining its silver reserves and causing financial instability and inflation. [35] The pervasive consumption of opium impaired the health and productivity of the population, deepening poverty and social unrest. [36] The unequal treaties imposed by foreign powers eroded China’s sovereignty, forcing the cession of territories like Hong Kong and opening numerous ports to foreign control. This undermined the Qing dynasty’s authority and led to internal rebellions. The increased foreign influence further diminished China’s control over its affairs, contributing to the eventual fall of the Qing dynasty and significant political and social upheaval. [37]
Modern Era
In the 20th century, the extraction of alkaloids from Papaver somniferum led to the development of various pharmaceutical opioids. Two key developments include:
- Morphine: Extracted from opium, morphine is about ten times more potent than crude opium. This breakthrough, achieved by German chemist Friedrich Sertürner in 1805, transformed pain management by providing a powerful and effective analgesic for patients undergoing surgery or suffering from severe pain. [38]
- Heroin: Developed by Bayer in the late 19th century as a supposedly safer alternative to morphine, heroin (diacetylmorphine) was initially marketed as a cough suppressant and a remedy for morphine dependency. However, it soon became evident that heroin itself posed significant risks. The realization of these risks led to the regulation and eventual prohibition of heroin and other opium-based preparations under various international treaties and national laws. [39]
These compounds revolutionized pain management. However, the high potential for misuse of these potent opioids led to widespread social and health issues, like the spread of infectious diseases through needle sharing. The first major international effort to control opium came with the International Opium Convention of 1912, which was the first international drug control treaty. Today, the cultivation and use of Papaver somniferum are highly regulated. International treaties, such as the Single Convention on Narcotic Drugs of 1961, aim to control the production and distribution of opium and its derivatives while permitting their use strictly for pharmaceutical applications. The convention mandates stringent regulations to ensure that the cultivation and processing of opium poppies are limited to licensed operations for medical and scientific purposes. [40] Poppy, along with coca and cannabis, is one of the only three plants subjected to such international regulation. [41]
Biocultural Sustainability
The opium poppy has deep-rooted significance in various cultures, particularly in South and Southeast Asia, the Middle East, and parts of Europe. Traditional practices involving the plant range from medicinal applications to ritualistic and culinary purposes. Maintaining these cultural practices while promoting sustainable agriculture ensures the preservation of both biodiversity and cultural identity. [42]
The opium poppy thrives in temperate climates and contributes to agricultural biodiversity. Sustainable cultivation practices are essential to prevent soil degradation and maintain ecological balance. Crop rotation and organic farming methods can help preserve soil health and reduce the environmental impact—such as high water consumption, soil degradation, and pollution from chemical fertilizers and pesticides—of poppy farming. [43]
Challenges
- Regulatory restrictions: There are strict regulations on opium cultivation due to its potential to contribute to substance use disorders. This can limit people’s ability to exercise their traditional and cultural practices. [44]
- Economic pressures: Farmers often face economic challenges that can lead to unsustainable practices or unregulated, underground cultivation. [45]
Strategies for sustainability
- Policy integration: Developing policies that balance control with allowing traditional practices can support biocultural sustainability. [46]
- Community engagement: Involving local communities in conservation ensures their cultural practices are respected and preserved. [47]
- Research and education: Promoting research on sustainable cultivation techniques and educating farmers about these practices can enhance both ecological and cultural sustainability. [48]
Chemical Composition and Dosage
The primary alkaloids in Papaver somniferum are morphine, codeine, and thebaine, which are potent analgesics that are extracted to make pharmaceutical opioids. Morphine is the most prominent, with its dosage being standardized in medical applications to ensure safety and efficacy. [49] Proper dosing is critical to manage pain while minimizing risks.
Benefits of proper dosing include optimal pain relief, enhanced patient safety, and the ability to customize and adjust treatment plans based on individual needs. It ensures that patients receive the right amount of medication for effective pain control without overmedicating. This can in turn prevent severe complications like respiratory depression. On the other hand, improper dosing can lead to significant risks including overdose, increased tolerance, dependency, and withdrawal symptoms. It is crucial to have careful monitoring and adherence to standardized dosing protocols. [50]
Whole opium resin contains a complex mixture of alkaloids. It is significantly different from isolated opiate extractions regarding dependency and overall effects. The whole resin’s blend of alkaloids can produce a more balanced pharmacological effect, potentially reducing the immediate intensity of euphoria and subsequent risk compared to isolated opioids like morphine. [51]
Isolated opiates, which are naturally occurring compounds derived from the opium poppy, are more potent and standardized. This can lead to a higher risk of rapid tolerance and dependency due to their concentrated nature. In contrast, the variability and lower concentration of active compounds in the whole resin might slow the development of tolerance and dependence. This happens because the exposure to active compounds is less intense and consistent. But it also makes it harder to control dosing and predict individual reactions. The variability in the composition of opium poppy extracts can lead to challenges in determining the precise amount of active ingredients, resulting in varied individual responses. However, for users of whole plant extracts, this variability is typically not a significant issue. Users can self-titrate their dose by adjusting the amount they consume based on their personal response. This method is effective with plant extracts but becomes problematic with pure or highly purified alkaloids, where precise measurement is crucial to avoid adverse effects. [52]
The term “opiates” specifically refers to natural derivatives of the opium poppy. “Opioids” is a broader term that includes both naturally occurring opiates and synthesized pharmaceutical products. Synthesized opioids —such as oxycodone, hydrocodone, and fentanyl— are chemically created in laboratories and designed to mimic the effects of natural opiates. While these opioids can be more potent and provide more consistent dosing, they also carry greater risks. [53]
- Morphine is the most potent analgesic extracted from the plant and constitutes about 10-15% of the raw opium. It is commonly administered in doses ranging from 5 to 30 mg, depending on the patient’s pain level and opioid tolerance. It can be given orally, intravenously, or through other routes.
- Codeine makes up approximately 1-3% of the concentration of opium resin and is known for its analgesic and antitussive properties. It is typically prescribed in doses of 15 to 60 mg for pain relief and cough suppression. It is available in tablets, syrups, and combination products.
- Thebaine is present in smaller amounts in the plant (0.2-1%). This compound is not directly extracted but instead is a precursor for synthesizing other opioids like oxycodone (a semi-synthetic opioid used for managing moderate to severe pain) and naloxone (an opioid antagonist used to counteract the effects of opioid overdose).
- Papaverine is employed for its antispasmodic effects, typical doses range from 100 to 300 mg per day.
- Noscapine is an antitussive (cough suppressant), dosages usually range from 50 to 100 mg per dose, up to 4 times a day. [54]
Dosage of raw opium
The intensity and composition of opium effects depend on the variety of Papaver somniferum, making precise dosing challenging. Raw opium is the dried latex obtained from the unripe seed pods of the opium poppy. When this latex dries and hardens, it forms a substance known as opium resin. Over time, residual water evaporates, meaning older, harder opium tends to produce more intense effects than fresher, softer opium.
Raw opium contains about 10-12% morphine by weight. A common initial dose of raw opium can be approximately 150-200 mg, which equates to 15-20 mg of morphine. An oral average dose is between 0.3 to 0.5 g. Opium dosages can vary significantly due to the differing quantities of active alkaloids in each batch. Oral ingestion carries higher risks as the dosage is less controllable compared to smoking. Consuming two grams orally can be fatal. [55]
Tolerance to opium develops quickly, so initial doses need to be smaller than subsequent ones. For first-time users, it’s advisable to start with a low dose and adjust based on the experienced effects. Smoking provides immediate effects. This makes it easier to control but also increases the risk of dependency. Oral consumption effects can take over an hour to appear and last up to 12 hours. If ingested, the effects are more intense and potentially surprising. This can increase the risk of overdose, especially if the product’s concentration is unknown. [56]
Smoked opium dosage is a match head-sized piece of the resin at a time, approximately 0.1 gram. The effects of opium are felt almost immediately when smoked. This makes it easier to determine a safe dosage. [57] Opium is not smoked but is rather vaporized. Its alkaloids vaporize at temperatures between 150-250º C.
Here is a general guideline for low, medium, and high doses:
- Low dose: 0.1 to 0.2 g.
- Medium dose: 0.3 to 0.6 g.
- High dose: 0.7 to 1.5 g.
- Fatal dose: 2 g. [58]
These dosages are approximate and can vary depending on the individual’s tolerance, the specific alkaloid content of the opium, and the intended purpose. Medical supervision is crucial to avoid overdose and severe side effects.
Effects
The alkaloids from Papaver somniferum provide analgesic, sedative, and euphoric effects by binding to opioid receptors in the brain and spinal cord. While effective for pain relief, some of the plant’s active compounds may carry a high risk of developing dependence or substance use disorder. Side effects may include nausea, constipation, and respiratory depression. Prolonged interaction can lead to the development of tolerance and withdrawal symptoms. [59]
Primary effects
- Analgesia: Opium provides significant pain relief, making it highly effective for managing both acute and chronic pain. [60]
- Euphoria: The activation of opioid receptors leads to a feeling of euphoria, a state of intense happiness and well-being. This is one of the reasons for people turning to it for recreational purposes and why it has the potential for dependency. However, research indicates that euphoria is not a universal experience among opioid users. The feeling of well-being often reported is more about relief from pain or distress. [61]
- Sedation: Opium acts on the central nervous system to produce sedative effects, leading to drowsiness and relaxation. This makes it useful for treating insomnia and anxiety in some contexts. This sedation can impair cognitive and motor functions, posing risks for activities requiring alertness. [62]
- Cough suppression: Codeine, an alkaloid in opium, is a well-known cough suppressant that is often an ingredient in medicinal cough syrups. [63]
- Effects on the cardiovascular system: Opium consumption is generally associated with cardiovascular outcomes, such as atherosclerosis, myocardial infarction, arrhythmia, low ejection fraction, and increased cardiovascular mortality. Some studies also suggest potential protective effects. [64]
Side effects
- Nausea and vomiting are common side effects, especially in individuals not accustomed to taking opioids. [65]
- Constipation: Opioids slow down gastrointestinal motility, which can lead to constipation especially when taken frequently. [66]
- Respiratory depression: High doses can significantly slow down breathing, which can be life-threatening. [67]
- Tolerance and dependence: People taking opiates frequently can develop tolerance (the need for higher doses to get the same effect) and physical dependence. This can lead to withdrawal symptoms if someone reduces or stops their dose suddenly instead of tapering off. [68]
Long-term effects
- Substance use disorder: The euphoric effects of opiates may lead to psychological dependence and substance use disorder, a significant public health issue. [69]
- Cognitive impairment: Chronic interactions with opiates can impair cognitive functions and judgment. [70]
- Physical health impacts: Long-term interaction with opiates is associated with various health issues, including hormonal imbalances and weakened immune responses. [71]
Legal Status
The legal status of Papaver somniferum varies globally. Many countries regulate or prohibit opium cultivation due to the potential for developing substance use disorder, although poppies are often allowed for culinary and ornamental purposes. International treaties like the 1961 Single Convention on Narcotic Drugs govern the production and distribution of opium and its derivatives. The regulation of opium is controlled by international treaties and national laws aimed at controlling its production, distribution, and use. [72]
International Treaties
- Single Convention on Narcotic Drugs (1961): This treaty, administered by the United Nations, is the cornerstone of the international control system for narcotic drugs. It classified opium as a Schedule I substance, indicating a high potential for abuse, and put it under strict regulation. Countries that are signatories to this treaty are required to limit the production, distribution, and use of opium to medical and scientific purposes. While not all countries are signatories, the majority of UN member states have ratified the treaty and comply with its regulations. [73]
- Convention on Psychotropic Substances (1971): While this treaty primarily focuses on synthetic psychotropic substances, it complements the Single Convention by ensuring comprehensive control over substances with abuse potential. [74]
- Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances (1988): This treaty establishes the obligation for states to classify in their domestic criminal law, and establish criminal sanctions to all activities related to the use, production and trade of substances controlled in the previous conventions (including opium). [75]
National Regulations
Some countries have implemented the required international treaties into their national laws and modified them. This created varied legal statuses for opium:
- United States: Opium is classified as a Schedule II controlled substance under the Controlled Substances Act. This allows for limited medical use with stringent regulatory controls. The cultivation of opium poppies to extract opium is illegal. [76]
- Mexico: Mexico remains a significant producer of opium, particularly in regions like the Golden Triangle and Guerrero. In this country, its production is also illegal. The Mexican government has engaged in extensive eradication campaigns, often supported by the United States. However, the economic reliance of many rural communities on opium poppy cultivation, coupled with the influence of powerful drug cartels, complicates enforcement. [77]
- European Union: Member states regulate opium under the guidelines of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). While some countries permit the cultivation of opium poppies for ornamental, pharmaceutical or culinary purposes, the extraction and use of opium are tightly controlled. [78]
- India: India is one of the few countries where the cultivation of opium poppies for medicinal opium is legally permitted under strict government control. The Narcotic Drugs and Psychotropic Substances Act regulates its production and ensures that it is employed for legitimate purposes. [79]
- Afghanistan: Despite international efforts to curb production as part of the global war on drugs, Afghanistan has been the world’s largest producer of underground opium production for decades. In 2023, opium poppy cultivation and opium production dramatically declined after the ban prohibiting “Poppy Cultivation and All types of Narcotics” was announced by the de-facto authorities (DfA) in April 2022. [80]
- Myanmar: Since 2023, Myanmar has become the world’s largest producer of opium, surpassing Afghanistan. In this country, the estimated opium yield reached approximately 1,080 metric tonnes in 2023, with substantial cultivation increases in regions such as Shan State. In Myanmar, opium production is illegal. However, enforcement is complicated by ongoing conflict and economic instability. [81]
- Australia: Australia has a licensed and regulated opium poppy industry primarily for the production of its alkaloids for pharmaceutical purposes. The cultivation of opium poppies is strictly monitored to prevent diversion into unregulated markets. [82]
Prevalence of Consumption
The prevalence of opium consumption varies widely across different regions and populations and is influenced by cultural, socioeconomic, and regulatory factors. Opium consumption is most prevalent in regions with long histories of cultivation and an ongoing traditional relationship with the plant, such as Asia and the Middle East. Modern trends indicate that opioid use disorder has become a significant issue in parts of North America and Europe, exacerbated by the ongoing opioid crisis. [83]
South and Southeast Asia
Countries like Afghanistan, Iran, and India have historically high rates of opium consumption. This is due to poppy being part of traditional practices and it being present in unregulated markets. Following the 2021 coup in Myanmar, economic and social instability drove many farmers to cultivate opium as a survival strategy. In 2023, Myanmar surpassed Afghanistan as the world’s largest opium producer with 47,100 hectares of the plant being cultivated with an average yield of 22.9 kilograms per hectare. [84]
Middle East
In Iran, opium has been part of traditional practices. Today it represents a significant public health issue. Before the 1979 Islamic Revolution, Iran cultivated up to 33,000 hectares of opium poppy, which was eradicated by 1980. However, this led to Iran becoming a major transit route for opium destined for Afghanistan and Pakistan. Despite strict anti-drug policies, Iran faces a severe opiate use disorder situation that affects nearly 2% of its population. The country leads the world in opium, morphine, and heroin trafficking seizures. Trafficking pressure remains high on its eastern borders. This has resulted in over 3,100 law enforcement deaths since 1979. [85]
North America and Europe
The Opioid Crisis in the United States, Mexico, and Canada has the most issues arising from opioid derivatives, including those coming from opium. The U.S. has had overdose deaths rise nearly sixfold since 2000. [86] There were over 106,000 deaths in 2021, mainly due to opioids like heroin, prescription painkillers, and synthetic opioids such as fentanyl. Fentanyl alone accounted for about 71,000 of these deaths. Other countries in the Americas such as Guyana, Bolivia, and the Dominican Republic also report high opioid-related death rates, although it is much lower than in North America (<2 per 100,000 people). [87] The fentanyl market is expanding across Latin America, with significant increases in seizures of medical fentanyl in countries such as Argentina, Colombia, Panama, and Brazil. [88]
While opium consumption itself is not as prevalent in Europe, opioid dependency remains a critical issue, often linked to heroin and prescription medication misuse. The European Drug Market report on heroin and other opioids stated heroin remains a major concern in Europe. It accounts for significant drug-related harms, including 74% of overdose deaths in 2021. The report indicated a stable heroin supply with rising purity and decreasing prices. Additionally, synthetic opioids such as fentanyl pose an increasing threat. This issue requires enhanced monitoring and international cooperation to address public health and security risks. The European Union is a key market and transit region for heroin and has around one million high-risk opioid users. However, fentanyl is increasingly appearing in European drug markets, often mixed with heroin or sold as a counterfeit medication. [89]
Health and Risk Reduction
It is crucial to implement risk reduction strategies to minimize harm when taking opium or products derived from the plant. [90] Key measures include finding the minimal effective dose and avoiding prolonged interaction to prevent developing dependency. [91] Recognizing early signs of opioid use disorder is also vital for timely intervention. [92] In the event of an overdose, immediate action with opioid antagonists such as naloxone is essential. Naloxone can effectively reverse the effects of an overdose and is a critical tool in emergency response. [93]
Additionally, it is crucial to avoid combining opioids with central nervous system depressants like alcohol or benzodiazepines. This can significantly heighten the risk of a potentially fatal overdose. [94] Ensure you do not take opioids in isolation—always inform someone about it.
For those who take unregulated opioids, it is advisable to test a small quantity first to gauge their potency and reduce the risk of overdose. Refrain from driving or operating any machinery after taking opioids to ensure safety. [95] To further reduce the risks associated with opium use, individuals can utilize safe consumption spaces where medical supervision is available. [96] Access to clean equipment is essential to prevent infections and other health complications. [97]
Peer support programs can provide valuable guidance and support from individuals with similar experiences. [98] Education on safe practices, such as using drug-checking resources to test for contaminants, can enhance safety. [99] Regular health check-ups are important to monitor and address any health issues that may arise from opium use. [100] By following these guidelines, individuals can significantly mitigate the risks associated with opium or opioids.
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