Ketamine withdrawal symptoms can manifest in a variety of intensities and durations, with significant variability between people. In one case, withdrawal symptoms were reported after only 12 days of regular ketamine use, although the amount regularly used was quite large. The severity of symptoms that developed after such a short period is concerning and illustrates the powerful addictive potential of this drug. The symptoms of ketamine withdrawal can range from merely uncomfortable, to potentially life-threatening. While there is currently a lack of thorough research on the effects of ketamine withdrawal in humans, we can look to a few case reports for a broad overview of the possible symptoms of ketamine withdrawal.
A general overview of the ketamine withdrawal timeline may roughly follow this course:
Due to the very short half-life of ketamine, within hours of the last time ketamine was used, withdrawal symptoms may begin to appear. The first ones to appear are often a tremor followed by intense anxiety and depression. These symptoms may escalate quickly and may be joined by a host of other uncomfortable, or even dangerous, symptoms.
The symptoms of ketamine withdrawal that may be expected during the first two weeks may include:
These symptoms are rarely dangerous in average, otherwise healthy ketamine users, but in the cases of heavy users or those with pre-existing health conditions, there may be an increased risk during withdrawal. Of particular note is the increased risk of dangerous complications for people who have pre-existing heart conditions. The sometimes sharp increase in heart rate can easily lead to dangerous and potentially fatal complications such as stroke and cardiac arrest if medical help is not provided. Another aspect to consider is the presence of mood swings and increased aggression. While this may pose indirect risks they could potentially be severe, both to the one experiencing these symptoms, and others nearby.
Since the timeline for ketamine withdrawal is still not well understood, it is unclear how long symptoms may persist into the third or fourth week of withdrawal. While the physical symptoms may be mostly resolved by this point, there may still be psychological symptoms that can persist up to this point and beyond.
Some of the symptoms of ketamine withdrawal that may persist through the third and fourth weeks may include:
The symptoms of ketamine withdrawal seem to vary greatly between individuals and this is due to multiple factors. Individual metabolism plays a large role as does liver health and function. Genetics may also play a role regarding certain genes and their relationship to metabolism. Additionally, the quality of ketamine is a large factor as well, as pharmaceutical grade ketamine is often of high quality, but illicitly produced ketamine can vary greatly in purity. This has to do with the fact that ketamine exists in two unique forms, (R) levo-ketamine and (S) dextro-ketamine, and these enantiomers have slightly different effects. These two forms are present in a roughly 50-50 ratio in pharmaceutical-grade ketamine but illicitly produced ketamine can have wildly varying ratios. The exact ratio of these different forms can greatly impact the potency of ketamine, thus the withdrawal symptoms may be more or less intense, and different symptoms may be present or absent depending on the ratio of these two distinct forms of ketamine.
Ketamine is a dissociative anesthetic and analgesic that is a derivative of the drug PCP. It is commonly used as anesthesia during surgery, most commonly in veterinary medicine, but also in humans. It is an effective option when full sedation is not required, such as setting a broken bone or thoroughly cleaning a burn. More recently it has also seen application as a painkiller for specific types of chronic pain, such as neuropathic pain conditions or hyperalgesia. The way ketamine works is quite unique among anesthetics and depressants, and it can selectively suppress certain functions while leaving others almost completely unaltered. Ketamine also produces dose-dependent effects, with smaller doses producing depressant effects and larger doses producing hallucinogenic effects. The exact way these hallucinogenic effects are produced is unclear, as ketamine interacts in fairly complex ways with a wide range of neurotransmitters in the brain.
The main mechanism of action through which ketamine produces its anesthetic and analgesic effects is through interaction with the glutamate neurotransmitter system. Glutamate is a major excitatory neurotransmitter in the brain that is responsible for maintaining a wide range of processes. Specifically, ketamine acts as an antagonist at NMDA glutamate receptors and acts to blockade these receptors which prevent them from being activated as they normally would. This leads to a reduced ability for signals to travel between certain parts of the brain, so while pain signals may reach the brain, they do not make it to a center of awareness, therefore are not perceived.
In addition to glutamate interactions, ketamine also interacts with the opioid system; more specifically it acts as an agonist (activator) at μ-opioid receptors and possibly δ-opioid receptors as well. These receptors are responsible for the perception of pain and interactions with these receptors are the main way that opiate drugs like heroin suppress pain. In addition, ketamine can produce interactions with the dopamine and serotonin neurotransmitter systems, although these interactions are not well understood. These neurotransmitters can produce pleasure and feelings of reward in the case of dopamine, and act as a mood regulator and elevator in the case of serotonin. Very recently, ketamine has been proposed as a treatment for refractory depression, although research into its effectiveness and safety is ongoing.
Through continued ketamine use, both the glutamate and opioid neurotransmitter systems can undergo a process known as upregulation (for NMDA glutamate receptors) and downregulation (for the opioid receptors). For glutamate, since ketamine blocks the activation of the receptors, the brain will increase its sensitivity to glutamate in an effort to compensate. A similar process can occur with the opioid system, although it is the reverse. Since ketamine activates the opioid receptors, the brain will reduce sensitivity to these receptors to maintain balance. This can occur in a fairly short time, often just a few weeks of regular or heavy use. Once downregulation has occurred, ketamine withdrawal symptoms will emerge when someone goes too long without using the drug.
The short answer: in most cases. While ketamine detox may not often be particularly dangerous in a direct and physical manner, the psychological symptoms can pose significant, although secondary, risks. Aside from the risks, detoxing from ketamine is oftentimes very uncomfortable. Entering a detox can not only minimize the risks, both direct and indirect, but these facilities can also reduce the discomfort of the experience.
Through the use of medications, medical supervision, and behavioral therapies these programs can offer support and care for both the physical and psychological symptoms. Medications and medical supervision can reduce the discomfort of the experience and the risks of dangerous complications. Behavioral therapies can help someone deal with the psychological stress and discomfort while also helping them to break old, unhealthy habits and to build newer, healthier ones.
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