The cocaine-e-cigarette – A theoretical concept of a harm reduction device for current users of smokable cocaine forms

Authors Fabian P Steinmetz, Heino Stöver Published October 16, 2021 Although there are great regional differences, smokable forms of cocaine (crack, free-base, paco, etc.) are a drug complex associated with often harmful and problematic drug use patterns. While strategies based on drug prohibition did not eradicate the consumption of smokable cocaine forms, prohibition itself led  …


Project Twenty21 - October Update

Get Project Twenty21 Updates via Email   We’re pleased to finally be able to announce that Attention Deficit Hyperactivity Disorder (ADHD) in adults has now been added to the list of indications covered by the study. This means that we will be able to start collecting data on how medical cannabis affects adults diagnosed with ADHD  …



chemical structure of phencyclidine (PCP) molecule

PCP stands for phencyclidine or phenylcyclohexyl piperidine, and is a dissociative anaesthetic (similar to ketamine) causing a wide range of effects including hallucinations, feelings of euphoria, and of being disconnected from one’s environment. Street names include angel dust, hog, and peace pills.

PCP was discovered in 1926 and was marketed as a general anaesthetic from the 1950s. It was limited to veterinary use in 1967 due to side effects in humans such as dysphoria, hallucinations and poor muscle relaxation. Veterinary use was also suspended in 1978 after the discovery of ketamine

Illegal production of PCP began in the 1960s and it emerged as a recreational drug. Recreational use became more widespread throughout the 1970s but has become less common since.

PCP can be found as an oil, liquid, powder, pill or crystal. It is most commonly smoked, often mixed with cannabis or tobacco, but can also be insufflated (snorted), taken orally (as a pill or powder), or injected.

When smoked with cannabis or tobacco, the usual dosage is 1-10mg of PCP, while tablets usually contain between 1-6mg. When taken orally or inhaled, 10mg of PCP can produce sedation, whereas when injected only 0.25mg is needed.

Taking PCP by injection is strongly advised against. This is because very low doses are required to cause effects meaning there is a higher risk of overdose.

As production is unregulated, it is difficult to know the exact dose being taken. There is also a poor relationship between PCP intoxication and the blood serum concentration of PCP in patients, meaning we have a limited understanding of safe doses of PCP. It is thought that doses greater than 10mg usually result in mild coma and doses of 25mg or more can result in deep coma, convulsions and even death.

PCP action is not entirely understood but is thought that it mainly acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, meaning the drug blocks the action of glutamate at NMDA receptors. PCP also stimulates an enzyme called tyrosine hydroxylase resulting in an increase in dopamine, norepinephrine and serotonin production. Dopamine and serotonin production is associated with many other hallucinogenic drugs and could be responsible for the hallucinations and euphoria caused by PCP. At high PCP doses, strong NMDA antagonism results in complete analgesia and anaesthesia.

The effects, onset time and duration are dependent on the dose taken and the route of administration.

 

Onset time:

Effects are usually felt anywhere between 15-60 minutes after oral consumption, but are felt just 2-5 minutes after inhalation.

 

Duration:

The effects of PCP usually last between 6 and 24 hours but could be up to 48 hours.

 

Effects:

The effects of PCP are numerous and highly variable but are often summarised using the mnemonic RED DANES: rage, erythema (red skin), dilated pupils, delusions, amnesia, nystagmus (uncontrolled lateral eye movements), excitation and skin dryness. Effects may vary depending on dosage.

 

Low doses (2-5mg, orally ingested):

  • Euphoria
  • Hallucinations
  • Dissociation – feeling of detachment from your body/surroundings
  • Sadness, anxiety, paranoia, confusion – often felt in waves
  • Numbness – as the analgesic effects begin
  • Unpredictable behaviour
  • Aggressive or violent behaviour
  • Reduced pain sensation

 

Moderate to high doses (5-25mg, orally ingested):

  • Confusion
  • Further reduced pain sensation
  • Stupor
  • Mild coma – often occurs at doses greater than 10mg

 

Very high doses (>25mg, orally ingested)

  • Convulsions – uncontrolled shaking
  • Deep coma with no response to pain
  • Death – can be caused by complications as a result of inhibited pain response (e.g. burns or drowning in a bath), violent behaviour, hyperthermia, hypothermia (e.g. falling asleep outdoors in cold weather), and breathing problems

 

Comedown: Some users may feel a comedown as the drug wears off. This may last for around 24 hours and feels similar to a hangover. Symptoms can include nausea, headaches and trouble sleeping.

 

Tolerance

Chronic users can develop a higher tolerance to PCP with frequent use, meaning that they need increasingly higher doses to experience the same effects.

Since the use of PCP as a medical anaesthetic for humans was replaced with Ketamine in 1965, and then later for animals, there have been no reported medicinal uses of PCP.

Some of the effects of PCP can have dangerous consequences, resulting in long-lasting mental effects, physical injury or even death. Although these usually only occur at high doses, it is important to know the risks.

 

Risks include:

  • Analgesia (loss of pain sensation)
    • This can lead users to hurt themselves, either intentionally or without knowing, and may mean that they do not seek appropriate help for an injury.
  • Violent/unpredictable behaviour
    • Violent behaviour is often reported in people intoxicated with PCP, and is one of the leading causes of death.
  • Cardiovascular effects
    • PCP can cause hypertension (high blood pressure) and tachycardia (fast heart rate). These are usually mild but can be severe in rare cases, and cardiac arrest has been reported following PCP intoxication.
  • Kidney damage
    • Rhabdomyolysis is seen in roughly 2.5% of people admitted to hospital with PCP intoxication. This is when myoglobin is released from the muscles into the blood stream causing damage to the kidneys, or even kidney failure.
    • The exact causes are unknown but could occur as a result of intense muscle contractions caused by PCP or due to PCP acting directly at the muscles.
    • Rhabdomyolysis can be identified by dark, reddish urine and sore or weak muscles and requires immediate medical attention.
  • Overdose
    • As previously mentioned, we have a poor understanding of safe PCP limits but it is suspected that doses exceeding 25mg can constitute an overdose.
    • Symptoms of an overdose include: agitation, nystagmus (uncontrolled side-to-side eye movements), prolonged coma, hypersalivation, hypertension, convulsions, opisthotonos (muscle spasms causing arching of the back and neck), respiratory depression and catatonia (awake but unresponsive).
    • Immediate medical attention is required if a PCP overdose is suspected.

Long term mental effects of PCP use include:

  • Chronic use can lead to acute anxiety, depression and psychosis.
  • Toxic Psychosis
    • Some PCP users experience psychosis after the effects of PCP have worn off. This can involve hallucinations, paranoid delusions and delusions of influence or religious grandiosity.
    • These symptoms often disappear after a few days but can last from weeks to months, requiring treatment. A psychotic state lasting for more than 2 months may indicate that a pre-existing psychosis has been exacerbated.
    • Schizophrenic-like syndromes have been reported in PCP users after chronic low-dose use as well as after single use.
  • Users have also experienced symptoms of frontal lobe syndrome such as speech impediments and memory loss long after taking PCP, as well as ‘flashbacks’, which is when users experience the feeling of being on PCP long after the drug has worn off.
  • PCP can cause changes in NMDA binding in the hippocampus that remain after PCP use. This may be responsible for altered speech and memory, and psychosis.

As PCP has a sedative effect, it should never be mixed with other depressants, such as alcohol, benzodiazepines or opioids, as this can increase risk of coma. Mixing with depressants can also lower your heart rate and breathing to dangerously low levels.

PCP can be addictive. Chronic users may find it difficult to give up and can develop a higher tolerance to PCP with frequent use meaning that they need increasingly higher doses to experience the same effects.

Addicts may also experience withdrawal symptoms when they stop taking the drug. Short-term withdrawal symptoms include high body temperature, seizures, agitation, muscle twitching and hallucinations. These effects can appear a while after the PCP wears off as the drug can remain in the body for around eight days. Long-term withdrawal symptoms may include depression, memory loss, cognitive dysfunction, impaired speech and weight loss.

We know little about whether any health conditions could make PCP more dangerous. However, there are a few pre-existing conditions that are suspected to increase the risk of some of the more dangerous effects of PCP.

It is suspected that a pre-existing psychotic disorder may increase the likelihood of toxic psychosis following PCP intoxication. It is also possible that other mental health conditions such as anxiety or depression could be exacerbated by PCP use. It has also been suggested that being prone to aggression could make PCP users more likely to exhibit violent behaviour while on PCP. Youth previous psychiatric problems may also be risk factors.

Little is known about whether pre-existing conditions of the cardiovascular system (e.g. high blood pressure, arrhythmias) can make PCP more dangerous. However as PCP is a cardiac irritant, users with conditions that put them at increased risk of cardiovascular problems should be cautious of using the drug.

PCP is classified as a Class A drug under the UK Misuse of Drugs Act and as Schedule II under the United States Controlled Substance Act. This means it is illegal to possess, supply or produce PCP in the UK and USA.

Low doses

PCP gets more dangerous with higher doses. Doses of less than 5mg are considered low and tend not to produce most of the more dangerous symptoms.

 

Sober sitter

The dissociation, hallucinations and delusions caused by PCP can be confusing. Taking PCP with a sober sitter present, rather than alone, can help users to maintain their grip on reality and manage dangerous or unpredictable behaviour.

 

Setting

PCP can cause unpredictable and potentially violent behaviour, and the loss of pain sensation can cause users to injure themselves. Staying in a safe and familiar environment, away from things that might cause injury can reduce the chance of harm.

 

Don’t combine with sedatives or depressants

As PCP can have sedative effects, combining with other sedative or depressants (e.g. alcohol, benzodiazepines, opioids) can increase risk of coma and cause depressed breathing and heart rate.

 

Know the signs of overdose

Symptoms of an overdose include: agitation, nystagmus (uncontrolled side-to-side eye movements), prolonged coma, hypersalivation, hypertension, convulsions, opisthotonos (muscle spasms causing arching of the back and neck), respiratory depression and catatonia (awake but unresponsive). If you recognise any of these in yourself or someone else, seek medical attention.

 

Stay hydrated

PCP can cause increased body temperature. Dehydration can be avoided by drinking water.

 

Don’t inject PCP

When taken by injection, very low PCP doses are required to cause effects meaning there is a much higher risk of overdose.

 

Don’t use often

Some of the more dangerous or long-lasting side effects of PCP become more common with frequent use.

PCP makes people violent

Violent behaviour is often associated with PCP use however the actual prevalence of PCP-induced violence is debated.

Many who disagree with the idea that PCP makes people violent point out that the majority of research into PCP and violence works with PCP users who have been incarcerated or hospitalized and could only represent the more extreme examples of PCP abuse. Additionally, when PCP users in the general population are studied, many authors agree that violence in PCP users is much less common than is portrayed in the media.

Some people also suggest that only certain risk factors cause PCP users to become violent while intoxicated. McCardle and Fishbein found that PCP users who exhibit violent behaviour tend to be younger, have more psychiatric hospitalizations and are generally more aggressive whether intoxicated or not.

There is limited research that investigates the connection between PCP use and violence, and studies often have methodological weaknesses and produce contradictory findings. Therefore we cannot determine the extent to which PCP induces or exacerbates violent behaviour and it is worth considering that this is still a possibility when taking the drug.

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chemical structure/skeleton of modafinil molecule

Modafinil (2-[(diphenylmethyl) sulfinyl] acetamide) is a manufactured drug that is a Prescription Only Medicine in the UK. It is available on prescription for a number of sleep disorders, such as narcolepsy. Although it is legal to possess, supply is illegal without prescription.

Modafinil has also become increasingly used as a recreational drug. Many students and professionals use the drug to improve their productivity and focus, as well as staying awake for longer. It has therefore been likened to drugs such as Adderall, Vyvanese and Ritalin which have also been used recreationally by healthy individuals to improve concentration.

Modafinil comes in the form of a white tablet. Typically, the drug comes in dosages of either 100mg or 200mg. The suggested daily dose for the treatment of narcolepsy is between 100-400mg.

The majority of recreational users report using 200mg as their preferred dose, with a few using up to 400mg, and some excessive dosages being 1000mg and over.

Modafinil is now off-patent and is available with a number of licensed ‘branded generics’ with their own trade names. Provigil is the main UK trade name, but modafinil is also available worldwide with a range of trade names such as Modalert, Alertec and Modavigil.

Armodafinil is a stereoismer of modafinil and is often marketed alongside or in replacement of modafinil. They have similar effects and are taken at similar dosages.

Modafinil is a stimulant. The exact way in which modafinil works in the brain is still relatively unknown as it has a complex mechanism of action. However, it is known that it acts on a number of neurotransmitters. It has been shown that modafinil works primarily through noradrenaline and dopamine transporter inhibition. It also acts on serotonin, histamine, gamma-aminobutyric acid and glutamate. Increases in the hypothalamic release of histamine also occurs as a result of modafinil’s action on the orexin system.

Physiologically, modafinil increases blood pressure and resting heart rate.

The onset time of the effects of modafinil can be anywhere between 30 and 90 minutes. The effects reach its peak between 2 and 4 hours after ingestion and can last between 12 and 15 hours. The main effects have been likened to a very high dose of caffeine. It is reported to improve concentration, decision-making and planning, whilst dramatically reducing tiredness.

As it is a stimulant, users of modafinil can experience similar adverse effects to other stimulants. These can include:

  • insomnia
  • headache
  • paranoia
  • irritability
  • stomach aches
  • loss of appetite
  • nausea
  • diarrhoea
  • weight loss
  • blurred vision
  • dizziness

In rare cases, a high dose of modafinil can also cause psychosis.

However, despite its pharmacological similarity to other stimulants, it has been reported that these effects are not as serious as other stimulants.

Modafinil has been used to treat narcolepsy since the 1980s. Narcolepsy is a sleep disorder that is characterised by excessive daytime sleepiness. Unlike with other stimulants  the use of modafinil doesn’t seem to lead to rebound (hyper) sleepiness when stopped.

Nowadays, it is primarily used as a cognitive enhancer, but has also been used by the military and those who have sleeping problems due to irregular work shifts.

There is also an emerging body of evidence of its usefulness in treating cocaine addiction.

Lastly, it has been shown that modafinil could be useful in treating disease-related fatigue, attention-deficit disorder, Alzheimer’s disease, age-related memory decline, depression, idiopathic hypersomnia, cognitive impairment in schizophrenia and myotonic dystrophy. However, evidence for its usefulness in treating these disorders is not yet significant enough to warrant its widespread use for them.

Modafinil has a half-life of 12 -15 hours, with the drugs main effects peaking at around 2 – 4 hours and then lasting for around 12 hours or more. Therefore, if a user experiences adverse side-effects, it can be particularly uncomfortable as these are likely to last for a long duration.

As it is a sleep-inhibiter, users can also experience sleep insomnia. Prolonged periods of sleeplessness can cause increased stress and will impair immune functions. It can also increase the risk of cardiovascular disease, diabetes, metabolic syndrome and depression. There is also a link between sleep deprivation and bacterial infections in the blood because of dampened immune responses.

The possibility of addiction to modafinil has been doubted by some with only a few cases having been reported.

However, because modafinil acts on neurotransmitters such as dopamine, it has been suggested that addiction is possible with modafinil because of its mood-altering effects.

There have also been a few reports of users experiencing withdrawal symptoms such as poor concentration, sleepiness, low energy, depression, anxiety and shortness of breath. These are, however, rare and in most cases very mild.

Not much is known about the long-term effects of modafinil. However, it has been demonstrated that prolific and prolonged use of the drug could cause serious disruptions to the users sleep architecture.

It has also been shown to have the effect of increasing dopamine in the brain, which contributes to abnormal dopamine function when not taking the drug. This could have long-term implications by increasing the potential for the drug to be abused by vulnerable users.

These long-term effects can also occur when high doses are used regularly.

Mental Health

Modafinil can cause anxiety, paranoia and jitteriness. Because of this, those with mental health issues such as anxiety, depression or a history of psychosis should be extremely cautious when using it.

Dosage

As the effects of modafinil can last for over 12 hours, any adverse effects might last a long time and so can become particularly uncomfortable and harmful. It is therefore a good idea to start with a low dose to get a better idea of the level of the users’ tolerance.

Oral Contraception

It has been shown that modafinil can reduce the effectiveness of the oral contraceptive pill. This reduced effect can also last 1-2 months after taking modafinil.

Appetite

Modafinil can also cause a decrease in appetite. Users should therefore ensure they are eating consistently throughout the day, and it is especially important that you are keeping well hydrated because dehydration can cause loss of strength, stamina and the exacerbation of common symptoms of stimulants such as anxiety, headaches, jitteriness and dizziness.

Insomnia

In order to counter the possible effect of insomnia, it is best to take modafinil at least 8 to 10 hours before the user plans on sleeping to ensure the main effects have sufficiently worn off.

Impurities

It is also illegal to supply modafinil without a prescription. However, many sellers advertise modafinil for sale without a prescription. These sellers are unregulated and so it is not possible to guarantee that it will definitely be modafinil that is being sold. As a result, users should always test their drugs before using them.

‘It can make you smarter’

Modafinil cannot make the user smarter. In the last decade, many students and working professionals have started to use the drug to increase the amount of work they are able to complete.

There is some evidence that it increases working memory, the users’ ability to plan and to concentrate better, however this does not mean you will automatically become smarter. In fact, some users have reported that instead of having increased concentration on their work, they instead concentrate on certain distractions like watching videos or using social media and struggle to get back to concentrating on what they intended to do.

Support our work and help ensure that evidence-based research can influence policy and public opinion, not political or commercial agenda.

Drug Science is an independent, science-led drugs charity. We rely on donations to continue to promote evidence-based information about drugs without political or commercial interference.

We are grateful … But we need more. We can’t do it alone. Becoming a donor will help ensure we can continue our work. Join our Community and access opportunities to become more deeply engaged in our work.

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