lundi 30 mai 2022

Research Chemicals: Tryptamine and Phenethylamine Use


Research Chemicals: Tryptamine and Phenethylamine Use


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Tryptamines and phenethylamines are two broad categories of psychoactive substances with a long history of licit and illicit use. Profiles of users of recently emerging tryptamines and phenethylamines are nonexistent, however, since surveillance studies do not query the use of these substances. 

This manuscript describes the types, modes of administration, onset of use, and context of use of a variety of lesser known tryptamines and phenethylamines among a sample of high-risk youth. Findings are based upon in-depth interviews with 42 youth recruited in public settings in Los Angles during 2005 and 2006 as part of larger study examining health risks associated with injecting ketamine. Youth reported that their use of tryptamines and phenethylamines was infrequent, spontaneous, and predominately occurred at music venues, such as festivals, concerts, or raves. Several purchased a variety of these “research chemicals” from the Internet and used them in private locations. While many described positive experiences, reports of short-term negative health outcomes included nausea, vomiting, diarrhea, disorientations, and frightening hallucinations. These findings, based upon pilot study data, move toward an epidemiology of tryptamine and phenethylamine use among high-risk youth.

MethodsThe use of tryptamines and phenethylamines among high-risk youth was discovered during a two-phase, three-city study examining health risks associated with injecting ketamine (see Lankenau, 2006; Lankenau et al., 2007; Lankenau and Sanders, 2007). Ketamine is a dissociative anesthetic that has emerged as a drug commonly used in the dance/rave scene (Jansen, 2001) and among subgroups of young IDUs (Lankenau et al., 2007). Phase one comprised a cross-sectional, ethnographic survey of young IDUs recruited in New York, New Orleans, and Los Angeles. Phase two consisted of a two-year longitudinal study of young IDUs recruited in Los Angeles during Phase one. Data described in this manuscript are largely based upon respondents recruited in Los Angeles; therefore, the discussion of methods primarily focuses on the Los Angeles site (see Lankenau et al., 2007, for a discussion of three-site methodology).

mardi 8 mars 2022

Opioids: understanding the current state in the UK

What is an opioid?



Opioids can either be sourced synthetically or derived naturally from opium; the latter are referred to as opiates. Examples of opiates include:


  • Morphine
  • Codeine
  • Thebaine

 

Heroin (diacetylmorphine) is an ester of morphine and being more natural than the semi-synthetics is still considered an opiate. Synthetic opioids include:

 

  • Tramadol
  • Methadone
  • Pethidine
  • Oxycodone
  • Fentanyl

 

Why are opioids prescribed?

Opioids are mainly prescribed for pain relief, for example, patients may have cancer and need end-of-life care. It is critical that they are as pain-free as possible. Other patients requiring opioids may have painful musculoskeletal disorders, some have acute post-operative, or post infarction pain. Another group require opioid-substitution therapy for drug dependence and addiction, and some may use opioids during the detoxification process.

Who is using opioids?

 

Interestingly, just seven countries, including the UK and the USA, use 77% of the world’s available morphine, depriving poorer countries of a ready supply.

 

While an essential element of pain-relief in some circumstances, it cannot be forgotten that these are dangerous drugs and over-prescribing may be contributing to a public health problem with enormous implications for clinical practice.

 

Last year alone in the UK:

 

    50 million prescriptions for opioids were written

    This is a 35% increase over 10 years

    Overdoses have increased by 87% to 12,000

    Deaths have increased by 41%, to 2,000 each year

    There are three times more deaths in the North East of the UK than in London, partly reflecting a greater usage of opioids amongst the socially disadvantaged

 

Opioid use and fatalities

 

Of the 115,000 prescriptions written every day, five result in a death.

 

Overall, the most widely prescribed opioid is tramadol, although for people presenting with musculoskeletal pain, 47% receive codeine, or one of its analogues, co-codamol or co-dydramol.

 

Tramadol filled the void left by coproxamol, when it was withdrawn around 2005. It is more likely to be prescribed by GPs than non-steroidal anti-inflammatory drugs (NSAIDs), due to the fact that the latter may cause complications especially in the older population. Tramadol may be perceived, in therapeutic terms, as lying somewhere between a weak and a strong opioid (an unhelpful distinction because this depends on dose), providing a false sense of security to prescribers hoping to avoid the stigma and risk of prescribing a ‘strong opioid’. Tramadol-related deaths amongst the opioid group increased from 9% in 2001 to 40% in 2011.

 

In 2017, the British Medical Journal (BMJ) published an interesting paper that focused on the opioid prescribing habits of 25 GP surgeries in London and the Midlands (Ashaye, et al., 2018). Researchers found that, of the 703 participants with musculoskeletal pain:

 

    59% were prescribed opioids

One quarter of participating patients were prescribed outside of National Institute for Health and Care Excellence (NICE) guidelines

Fewer than three prescriptions were given to individuals each year

 

There is no real definition for ‘over-prescribing’. Patients want pain relief, and social media platforms are awash with indignant sufferers attesting to their dependent but not ‘addicted’ status, because they have been relatively pain-free for so many years. Over 1.5 million people with musculoskeletal problems receive opioids, and according to guidelines, 45% are over-prescribed, at a loss to the NHS of £100 million per year. This does not include the cost of managing the side effects of opioid addiction or reliance, or of treating people who have overdosed.

 

Fatalities from recreational opioid misuse are now overshadowed by medically prescribed opioid-related deaths. In the US, this accounts for 60% of opioid-related deaths. However, the opioid problem in the US is not remotely comparable with the situation in the UK. As yet, we do not have marketing that directly promotes opioids to individuals, and our GPs do not receive huge financial incentives for prescribing particular drugs. Nevertheless, the prescription of opioids has increased by 60% in the last 10 years.

 

According to the Office of National Statistics (ONS):

 

    There were 4,359 deaths from drug poisoning in 2018

    This is up 16% from the previous year and is the highest annual increase since records began in 1993

    Deaths amongst men increased from 89.6 per million in 2017 to 105.4 per million in 2018 - two thirds of these were linked to the misuse of drugs

    Opioids, such as heroin and morphine, continue to be the most frequently mentioned substances on death certificates

 

Mixing opioids with other drugs

 

Incidentally, deaths involving cocaine doubled between 2015 and 2018. It is often impossible to tell the primary substance, as alcohol is frequently involved, and many people taking opioids are also using cocaine and other drugs, especially benzodiazepines. Since 2006, over half of all drug-poisoning deaths have involved opioids.

 

Any appearance of a decline in drug-related mortality is linked to a fall in cannabis usage. The addition of poly-substance misuse, club drug culture, chemsex, and new psychoactive and illicit substances (formerly known as ‘legal highs’), have only served to muddy the waters. With opioid-related deaths, toxicity is often not clearly related to dose as chronic use leads to tolerance. However, even if alcohol is present, the primary cause of death linked to an opioid is usually clear.

 

With the addition of cocaine, everything changes. Death may be due to serotonin syndrome or to hyperpyrexia. These cannot be diagnosed at post-mortem examination. Unless there is a cocaine-induced myocarditis, or an associate fulminant hepatic failure, the cause of death relies on eliminating other possible causes.

Just how strong is fentanyl?

Despite dire warnings from the US, and a blip here in 2017, deaths from fentanyl have remained relatively stable – 74 in both 2017 and 2018. It is likely that the analogue, carfentanil, contributed to most of these deaths. Police investigations uprooted a number of ‘dark web’ vendors who were subsequently arrested. Since then, there has been a dramatic decline in the number of deaths.

 

Fentanyl may be 80 times more potent than morphine.

 

Carfentanil may be many thousand times more potent still, and even 2mg can be fatal.

 

Respiratory depression and death can occur in under two minutes, as opposed to 20 or 30 minutes for heroin, giving time for the user to be treated. The prescription of ‘take-home’ naloxone must be considered here.

Multi-faceted treatment

 

The 2017 Drugs Strategy aimed to reduce the demand, restrict the supply and improve recovery by enhancing the quality of treatment and outcomes. The strategy asked for global action and new initiatives to respond to the emergence of new psychoactive and illicit substances.

 

The Care Quality Commission (CQC), recognising that opioid-related death was the third most common cause of preventable death for 15 – 49 year olds, asked that treatment be safe, effective, caring, responsive, and well-led. Treatment was found to be well-evidenced and to provide value for money. Every £1 spent on structured drug therapy saved the local society £2.50.

 

Unfortunately, the government’s attempts to reduce the supply of legal opioids has driven users back to street heroin, itself much cheaper and widely available. In one year, treatment presentations for opioid drug misuse has climbed from 120,000, to 250,000. Of these, 140,000 were linked to opioids and almost half (2/5) were for primary heroin use.

 

Treatment needs to be structured with:

 

  • Goal-setting and planning
  • Feedback and monitoring
  • Social support
  • Contingency management

    Cognitive behavioural therapy (CBT) and motivational interviewing are encouraged, along with evidence-based psycho-social interventions

 

In December 2018, Jeffrey Singer of the Cato Institute dared to reintroduce the policy of ‘harm reduction’. His paper, Shifting the war on drugs, to the war on drug-related deaths (policy analysis 10858), quoted my own papers published with Nicky Metrebian, as far back as 1998, and 2001, suggesting that it was feasible to prescribe opioids safely to some users and thereby to reap health and social gains. Others take this even further; states in the US where cannabis is legalised have a 25% lower rate of opioid painkiller overdose deaths. It may be asked: ‘is it time to look at cannabinoids as a reasonable substitute for opioid pain relief?’

 

Adverse effects of using opioids for pain management

 

Overall, there is a lack of evidence supporting the efficacy of opioid prescribing in the management of non-malignant pain. Treatment with opioids can lead to a plethora of adverse effects, including depression, anxiety, headache, hyperalgesia, inadvertent overdose, diversion, coma, and even death.

 

Remember:

 

    Prescribing daily oral morphine equivalents of between 50 and 99mg increases the risk of overdose by 3.7 times

    Prescribing over 100mg of morphine equivalent increases the risk of overdosing ten-fold

References:

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Research Chemicals: Tryptamine and Phenethylamine Use

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