• Dissociative Hallucinogens

  • These chemicals work to reduce the chemical action of glutamate. They simulate the negative and positive symptoms of schizophrenia.
    • Ketamine
      • Ketamine is the most addictive. Originally lauded as a “horse tranquilizer”, it is now recognized for rapid antidepressant effects. That said, it can cause serious neurological issues when abused. People have lost their bladder over an addiction to ketamine. Others suffer permanent and persistent hallucinogenic effects from abuse. Ketamine acts on the opiate receptors and as an SNDRI.

There seem to be neurological damage at play, too, as

Brain damages in ketamine addicts as revealed by magnetic resonance imaging (2013) reveals. Use was ~one gram per day for three or more years

Damage “included diffusely many regions: frontal, parietal, occipital cortices, parahippocampal gyrus, striatum (including caudate), cerebellum, and brainstem.”

Image B is a normal brain. Image A was imaged after half a year of ketamine addiction. The lesion and atrophy in image A was of prefrontal nature – the prefrontal cortex being a brain region of higher cognition. After three years, things get much worse. After seven years, toxicity is widespread and significant.

  • PCP
    • Not used very much these days, PCP is also a DRI. It has typically been used by gangs in warfare, as it acts to greatly release pain of wounds, evena  gunshot wound. People can become very spychotic in abusing this chemical.
Phencyclidine, also known as PCP, can cause a host of problems in simple use.

Studies on the substance concur that it is definitely neurotoxic, mostly affecting the cerebellum, which hosts the majority of neurons in the brain.

  • Dextromethorphan
    • Used to quell significant coughing, this chemical can create a dissociative effect in very high doses. These days, the cough liquid has another anti-cough chemical included so as to provoke vomiting if used in high enough doses to produce this psychoactive effect.

Yes, people actually die from abusing it.

  •  MK-801
    • This chemical in particular is used to simulate the positive and negative symptoms of schizophrenia in laboratory studies. It is also abused for its dissociative effects.

Investigation of Mechanisms for MK-801-Induced Neurotoxicity Utilizing Metabolomic Approach (2015) discovered:

“MK-801 induces NO and ROS production in the RS/PC region, which might subsequently induce oxidative stress and in turn neuronal cell death. In addition, MK-801-induced NO production increased glucose utilization and affected glucose metabolism, the imbalance of which might generate additional oxidative stress related to neuronal cell death.

  • Other GABAergics (substances that promote the activity of GABA)

    • GABA is the chemical that is responsible for lowered inhibitions in drinking alcohol, and the anxiolytic (anxiety-reducing) effects of benzodiazepines. Before benzodiazepines, there were other classes of GABAergics (substances that increase levels of GABA) used for anxiety disorders. Benzodiazepines are superior, yet it wasn’t until the 1950’s that the first benzodiazepine was marketed.
    • Importantly, GABA doesn’t only lower anxiety. It also relaxes muscles, promotes sleep, and can cause amnesia in very high doses. The muscle-relaxant effects are also why too fast of a withdrawal from GABAergics can cause seizures and death. This is why one must be tapered off of these substances after long-term use.
      • Bromides
        • These substances were routinely used through the late 1800’s.
        • They had hypnotic (sleep-inducing) and antiepileptic (seizure-reducing/muscle relaxing) effects
        • Unfortunately, bromide are highly toxic. This is both to the brain and the digestive system. Irritation, delirium, and hallucinations were also observed as side effects.
      • Choral Hydrate
        • In 1869, the effects of this substance were discovered.
        • Hardly in use in contemporary times
      • Barbiturates
        • 1864: firs synthesis
        • 1879: synthesis perfected
        • First one, barbital, was marketed first in 1904
          • Used for insomniacs (those who have trouble sleeping), manic episodes, and those with epilepsy
        • From the 20’s through the 50’s, this class of chemical was used en masse
        •  Over 2,500 such substances synthesized
        • Very unsafe medications
        • These days…
      • Meprobamate
        • Marketed as safer than barbiturates
        • Works against anxiety, as other GABAergics, and partially against epilepsy
        • Phased out after the discovery of benzodiazepines
      • Methaqualone
      • Z-drugs
        • “non-benzodiazepines”
        • Said to be selective for the α1 region of the benzodiazepine site
        • Initially thought to not have the abuse potential of benzodiazepines, later proved false
        • Stephen Stahl, the most celebrated psychiatrist, stated that tolerance to the hypnotic effects of these drugs does not decrease over time, as does with benzodiazepines
        • Can drastically reduce quality of sleep if abused
        • Zolpidem
        • Zaleplon
        • Eszopiclone
  • Other stimulants

    • “Bath Salts”, or, “Plant Food”
      • Derivatives of cathinone, the main stimulating chemical in the khat plant 
      • Little to no research on safety
      • Structural similarities to meth/amphetamine
        • Similar in action, as well
      • First users reported around 2005
      • 2010: first report of poisoning
      • 2011: explosion in media coverage

Image result for MDPV toxicity

    • Bupropion
      • Prescription antidepressant
        • Used for bipolar depression
      • Also shares the stimulant chemical backbone
      • Prescribed to aid smokers quit
      • Lowers the seizure threshold (decreases amount of stimulation to have a seizure)
      • Frequently abused in prisons
  • Kratom

    • A plant
    • Native to Southeast Asia
      • Very illegal, ironically, in its natural habitat
    • Not regulated in the United States
    • Mechanism
      • As related by Pharmacology of Kratom: An Emerging Botanical Agent With Stimulant, Analgesic and Opioid-Like Effects
        • More than 20 active compounds 
        •  Activates the μ, δ, and κ opioid receptors
        • Promotes activity of norepinephrine and serotonin
        • Decreases activity of the -5-HT2a receptor
        • Perhaps decreases acetylcholline release
        • Stops the muscarinic acetylcholline binding to its receptor
        • Works on a2 autoreceptor action
          • Activated autoreceptors reduce output of norepinephrine
    • Extracts exist, but usually comes as powdered plant material
      • This is swallowed
    • Can be just as addictive as classic opioids
    • As unregulated, there is no guarantee of contents, nor of strength
      • And little research, partly because plant-based medicines aren’t very profitable for pharmaceutical corporations

Mixing Gabapentin and Opioids

      • Oftentimes used for apparent anti-addiction properties
        • Opioids
        • Cocaine

        Image result for gabapentin pregabalin addiction

      • Little is known of how it works
      • It may be a depressant, but is not viable for tapering off of GABAergic substances
        • Experts disagree on its nature and/or degree and mechanism of GABAergic effects.
      • Can cause much physical dependence
        • Ashwoodrecovery.com lists withdrawal effects in abuse
          • Anxiety
          • Insomnia
          • Nausea
          • Vomiting
          • Sweating
          • Loss of appetite
          • Uncontrollable crying
          • An increased response to pain
          • Headaches
          • Fatigue
          • Irritability
          • Restlessness
          • Seizures

Image result for synthetic cannabinoids


Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2424120/, https://slideplayer.com/slide/5258345/, https://847j5msnmy-flywheel.netdna-ssl.com/wp-content/uploads/2018/01/Kratom-Infographicfinal.png, https://www.ashwoodrecovery.com/blog/gabapentin-opioids-killer-combo/, https://www.northpointwashington.com/blog/gabapentin-neurontin-abuse-not-likely-still-happening/