Within the ketamine users group, adolescent onset users were compared to adult-onset users. The included studies described structural gray matter and white matter differences, differences in brain functionality and differences in neurotransmitter receptor binding. The most frequently reported side effects of short term ketamine (hours/days) are related to the nervous system, such as dissociation, sedation, headache, dizziness, blurred vision and memory impairment (Short et al., 2017). The studies that have been done, have been conducted in clinical setting, with a much lower dose than the doses that are used recreationally. Given the effect that long-term ketamine exposure may yield, an effort should be made to curb its abuse.
During the COVID-19 pandemic, the DEA loosened its restrictions, allowing for prescribing of Schedule III substances like ketamine via telemedicine—but not including Spravato. Spravato rules mandate that the drug cannot be taken at home. They are also counseled on the risks of engaging too soon in activities requiring full alertness; for example, they are advised to avoid driving until the day after treatment. Patients are monitored for sedation, blood pressure, and possible dissociation during treatment and observation. In 2023, the National Academy of Medicine awarded Dennis Charney, John Krystal, and Husseini Manji the Sarnat International Prize in Mental Health for their discovery leading to esketamine. This discovery sparked additional psychiatric research on ketamine.
Ketamine‐An Update on Its Clinical Uses and Abuses
In lower doses, some people report positive experiences like enhanced creativity. does reese witherspoon have fasd Due to its dissociative properties, the most common short-term side effect of ketamine is hallucinations. A doctor or addiction specialist can help tailor a suitable treatment plan for your needs.
Long-term effects are cognitive and memory deficits, ulcerative cystitis, and abdominal complaints. Its effects are mostly the direct result of NMDA-receptor inhibition, although it also influences catecholamine reuptake and dopamine activity. Usually snorted, the effects of ketamine are quick and short lasting. Its potential for recreational use was discovered soon, which led to a surge in misuse in the 1990s. The GP undoubtedly has an important role to play in encouraging patients to quit ketamine use and in supporting cessation with follow-up visits or referral to specialised centres (Box 1). GPs should be able to recognise the specific signs of acute and chronic ketamine misuse.
Ketamine addiction
Given the limited number of included studies and diversity of outcome measures in the studies, the data was deemed not suitable for meta-analysis. The results were subdivided into structural differences in gray and white matter, functional differences and effects on neurotransmission. The quality of the studies was assessed using the Sackett Scale and the Oxford CEBM levels of evidence scale (Sackett, 1989; Howick et al., 2018). Finally, we found our complete dataset consisting of 16 studies (see Figure 1) for the inclusion flowchart.
The “K-Hole” Experience
- Esketamine was approved as a nasal spray for treatment-resistant depression in the United States and elsewhere in 2019.
- For children experiencing severe asthma exacerbations, intravenous ketamine led to prompt improvement and avoid the need for mechanical ventilation 64.
- In Australia, 300,000 people said they used ketamine in the previous 12 months, compared to 70,000 in 2016.
- The discovery of antidepressive action of ketamine in 2000 has been described as the single most important advance in the treatment of depression in more than 50 years.
- The actor had been using the drug through his regular doctor in a legal but off-label treatment for depression, which has become increasingly common.
- Activation of N‐methyl‐D‐aspartate (NMDA) receptor played an important role in the development of perioperative nociception‐related neural sensitization, hypersensitivity, and opioid tolerance 73, 74.
These investigations demonstrated ketamine’s short duration of action and reduced behavioral toxicity made it a favorable choice over phencyclidine (PCP) as an anesthetic. After promising preclinical research in animals, ketamine was tested in human prisoners in 1964. The presence of norketamine, a pharmacologically active metabolite, is useful for confirmation of ketamine ingestion. Urine is often the preferred specimen for routine drug use monitoring purposes.
What are the signs of ketamine addiction?
A study with 34 chronic ketamine users and 19 healthy controls found lower gray matter volume in the right insula, the left dorsolateral prefrontal cortex (DLPFC), the rOFC and the left inferior parietal cortex in ketamine users compared to controls (Hung et al., 2020a). Different from other studies, this study also found higher gray matter volume in ketamine users compared to controls, i.e., in the left caudate nucleus. The search concept combination can be displayed as ketamine AND (chronic OR long term OR abuse OR dependence OR known long term use effects OR induced adverse effects). Although we did not exclude studies in which subjects also used other drugs, we considered the limitation that differences other than ketamine use alone could exist between ketamine users and control subjects, including use of other drugs.
- Schedule III substances are defined as those that have moderate to low potential for physical and psychological dependance.
- An enantiomer of ketamine – esketamine – was approved as an antidepressant by the European Medicines Agency in 2019.
- Especially in children with tonsillectomy, difficulty swallowing, mainly caused by severe pain, could result in decreased food intake and subsequent dehydration.
- Also, why use an intravenous or injected ketamine instead of intranasal Spravato, with its precautions?
- Interestingly, ketamine psychotherapy has been suggested to be a promising approach to treat addiction of other drugs.
- Due to the bronchodilating properties of ketamine, it can be used for anesthesia in people with asthma, chronic obstructive airway disease, and with severe reactive airway disease, including active bronchospasm.
- This also explains why oral ketamine levels are independent of CYP2B6 activity, unlike subcutaneous ketamine levels.
Very‐low‐dose ketamine (0.05 mg/kg/h) has shown better early postoperative pain relief in patients undergoing open thoracotomy. Therefore, ketamine, a noncompetitive NMDA receptor antagonist, has analgesic, antiinflammatory, and antihyperalgesic effects. In addition to adult patients, children with bipolar disorder also showed significant improvement in mood and behavioral symptoms after intranasal ketamine administration 59. A rapid antidepressant effect of ketamine infusion maintaining for 2 weeks was observed in a considerable proportion of patients with bipolar depression 57.
There is no safe amount of ketamine people can use outside a medical setting. Despite this, many people use ketamine recreationally. Today, medical experts are exploring the use of Ketamine in the treatment of depression and other mental health conditions. This potent prescription drug has a significant risk of abuse, addiction, and life-threatening health consequences.
Pore blocking of the NMDA receptor is responsible for the anesthetic, analgesic, and psychotomimetic effects of ketamine. Cognitive deficits as well as increased dissociation and delusions were observed in frequent recreational users of ketamine. A 2019 large-scale study found that cannabis withdrawal management written reports of ketamine experiences had a high degree of similarity to written reports of NDEs in comparison to other written reports of drug experiences. The typical symptoms of ketamine-induced cystitis are frequent urination, dysuria, and urinary urgency sometimes accompanied by pain during urination and blood in urine.
The following results revealed that ketamine administration altered glucose metabolism in areas known to be involved in mood disorders; these alterations may partially underlie ketamine’s mechanism of action. It is characterized by recurrent episodes of elevated mood and depression, together with changes in activity levels 55. Bipolar (affective) depression, originally called manic depressive illness, is one of the most challenging psychiatric disorders to manage 54. Neurocognitive performance such as attention and memory improved significantly after completion of six ketamine infusions in TRD 50. Third, ketamine had an impact on increased wish to live and decreased wish to die, which were two cognitive aspects of suicide ideation. In all age groups, severity of depression improved with medication and was significantly related to suicide ideation or behavior.
A plasma metabolomics study in 22 BD patients demonstrated that the greater plasma concentration of D‐serine (D‐Ser) was a contributing factor to the antidepressant response after ketamine infusion 53. For individuals with major depressive disorder, response rates to ketamine at 4 h and 24 h were 56% and 71%, respectively, while for patients with bipolar depression, response rates at 4 h, and 24 h were 61% and 41%, respectively 51. Furthermore, numerous studies revealed ketamine possibly exerts its antidepressant action through interaction with 5‐HT2A receptors, which are known to play an important role in the pathogenesis of major depressive disorders 39, 40. Mechanistic studies suggested that ketamine inhibition of NMDA receptors leads to glutamate release and the activation of other glutamate receptors 34. Further investigation with randomized, controlled clinical trial is necessary to firmly establish the oral efficacy of ketamine for the treatment of depression. Recently, a larger open‐labeled trial with 14 patients demonstrated there was significant improvement in depressive symptoms after these patients received daily oral dose of ketamine over a period of 28 days 30.
Lastly, ketamine increases synaptic catecholamine levels by blocking the reuptake of norepinephrine into what is whipit presynaptic sympathetic neurons 71. First, NMDA receptors exist in the airway, and their activation seems to be linked to the release actions of sensory neuropeptides resulting in increased airway tone. For children experiencing severe asthma exacerbations, intravenous ketamine led to prompt improvement and avoid the need for mechanical ventilation 64. The first example using ketamine successfully to avoid the need for mechanical ventilation was described by Strube and Hallam 63 A 13‐year‐old girl with severe asthma regained consciousness 30 min after continuous intravenous infusion of ketamine.
Studies have found that for some patients, ketamine can begin to relieve their depression symptoms in a matter of hours after therapy and other medications have failed. The increases were similar for both people with depression and people without, suggesting that the growth is being driven by both more people seeking ketamine for clinical purposes and more people using it recreationally. On the other hand, as highlighted in the Times’ report alleging that Musk was mixing ketamine with other drugs, more Americans appear to be using ketamine recreationally and outside of medical supervision. It should be noted that in some studies, ketamine users had a mood disorder and for many of the studies it was unclear whether the ketamine users were diagnosed with another substance use disorder or another psychiatric illness. In one of the included samples, 50% of ketamine users had also been using heroin, which could have contributed to the observed brain changes (Sanacora and Schatzberg, 2015; Chesters et al., 2016). The results have been obtained from recreational ketamine users for whom we do not precisely know what dose of ketamine they used, which type of ketamine (racemic or esketamine) and whether they consumed pure ketamine or ketamine contaminated with other substances.
