Cannabis is a psychoactive drug derived from the dried leaves and flowers of the cannabis plant. It contains over 400 chemicals. The main active ingredient of these is THC (tetrahydrocannabinol). Overstimulation of the endogenous cannabinoid system with marijuana use causes changes in the brain that can lead to addiction in the process. The person in such a situation begins to determine his priorities according to cannabis and even if it causes negativity in his life, he cannot prevent its use. When the person decides to quit using cannabis, then he/she enters a period called cannabis withdrawal.
Especially in the first two weeks after quitting cannabis, irritability, restlessness, tremors, sweating, fever, decreased appetite, difficulty sleeping, digestive system problems (such as diarrhea or constipation), unstable mood, irritability, etc. may be observed in people who use cannabis intensively. Since some users experience milder physical withdrawal symptoms (sometimes associated with depression) when cannabis is quitted, it can be overlooked by the user. Despite this, craving, which users often describe as a “habit” or “psychological addiction,” is often seen. Contrary to popular belief, this situation is at least as biological as the physical withdrawal symptoms.
Withdrawal Symptoms as a Result of Cannabis Use
The rhetoric that cannabis is harmless and the misperception created as a result is frequently encountered today. Unfortunately, this perception can cause cannabis to be the preferred substance in the process of starting substance use. Cannabis, which is becoming more and more common, is an addictive and highly harmful substance like all other substances.
Especially in adolescents, cannabis use can be encountered due to situations such as curiosity, wannabe, excitement seeking, problems in family relationships, and nervousness. At the same time, the development of technology and the fact that we have access to a lot of information on the internet increase the awareness and accessibility of cannabis day by day.
Another important issue to be known about cannabis is that, as in all addictions, cannabis addiction can bring some withdrawal symptoms with it. If the cannabis addict does not use the substance that he/she has been addicted to for a certain period of time, cannabis, we can see symptoms such as:
- Sleep problems (Continuous sleepiness, disruption of sleep patterns)
- Inability to relax
- Anger Management Problems
- Demotivation Syndrome (Laziness)
- Memory impairments
- Problems with focus
- Skepticism (Paranoia)
- The tendency to act without thinking about the end
These symptoms may not be seen at the same time. Withdrawal symptoms are expected to appear within 6 weeks after you stop using cannabis, and this time can vary from person to person. We can also see many of these withdrawal symptoms when the person is using the substance regularly.
While some users see these withdrawal symptoms after a few hours of cannabis use, in others we can see them days later. These withdrawal symptoms are, like some other substances, tremors, diarrhea, pains, etc. We may underestimate or not notice these symptoms because they are not as severe. However, these should be taken as seriously as the deprivation created by other substances. When such situations are observed, the person should be intervened.
Substance use is addictive regardless of the substance used. Users with these symptoms have a high risk of becoming addicted. What we need to do is not to take cannabis use lightly and take precautions against possible future consequences.
If any of the withdrawal symptoms mentioned above are seen, medical support is recommended. In such cases, it is necessary to consult a doctor. Regular use of medication on the doctor’s recommendation to purify the body from deprivation helps the person to get rid of these symptoms more quickly and easily.
The treatment of addiction is a whole. Work should be done on not only withdrawal symptoms but also on prevention of reuse, as well as regaining the life order of the person, such as social support and recreation. Although medical support plays an important role in the healing process, psychological support should also be provided to the person.
What Is Cannabis Addiction?
Cannabis, known to be grown and used throughout history, is one of the most widely used substances. It is produced from Cannabis sativa, the cannabis plant used in the Far East for more than 4000 years. The most effective form is found in the dry, brown-black resin part of the poppy plant. Its use is by crumbling after being cut and dried, wrapped in a cigarette, and smoking.
Another way of use is to inhale the steam with the method called bucket or bong. There are also uses such as mixing it into a cake or drinking it as tea. Terms such as marijuana, tea, weed, and Mary Jane are used for cannabis. Names such as hemp, bhang, ganja, dagga, and sinsemilla are used to express its hardness.
When cannabis is used in cigarettes, its effect is seen within a few minutes; The effect of cannabis, which has the highest effect in 30 minutes, ends after 2-4 hours. Some of the mobility and mental effects can last up to 12 hours. Cannabis is consumed orally by putting it in food other than cigarettes. When the consumption of cannabis is at stake with the inhalation of smoke, a higher proportion of cannabis is used than the amount taken orally.
Effects of Marijuana vary depending on the strength of cannabis, the method of use, the method of intake, the place of use, the last experience of the users, their expectations, and the biological predispositions of the individuals. The use of alcohol or other substances which are taken while consuming cannabis also affects the effect of cannabis. Marijuana use causes a change in perception, short-term euphoria and relaxation, exaggeration in sensory experiences, and deterioration in time perception.
After use, there is an increase in activities such as watching movies or listening to music, eating too much. Marijuana is a gateway to other substances. Studies show that marijuana use increases a person’s potential to become addicted to substances as well as to abuse other substances. Dry mouth, hunger, redness of the eyes, increased blood pressure and palpitations are the most common side effects associated with the use of cannabis.
In continuous use, a decrease in testosterone level and sperm amount and a decrease in the fertility function of women are also among the side effects seen. While some individuals experience reactions such as anxiety, increased feeling of fear, panic attack; some individuals slow down. It also causes mental and physical disorders such as restlessness, difficulty sleeping, decreased appetite, weight loss, impatience.
After using cannabis, individuals laugh unnecessarily when they are under the influence of the drug, or it is observed that they are afraid and in a state of panic. Problems with balance, redness in the eyes, memory weakness, and weakening of reactions are other symptoms observed.
After the effect of cannabis wears off, the person experiences fatigue, sleepiness, and anxiety. Depending on the use of cannabis; disturbances in feelings and thoughts are particularly common side effects. There are withdrawal symptoms such as hypersensitivity, irritability, irritability, restlessness, decreased appetite, gastrointestinal disorders, fever, nausea, tremors, insomnia, and loss of sense of direction. Individuals with long and long marijuana use have hallucinations, confusion, and emotional disturbances that occur suddenly and last for a few days. Cannabis also appears to reduce the volume of the brain and cause brain damage.
Treatment of Cannabis Addiction
Cannabinoid receptors in the brain are more intense in the regions responsible for functions such as pleasure, memory, thought, concentration, sense, time, perception, and motor movement. Therefore, cannabis shows its effect mostly in these areas. Within half an hour of smoking marijuana, it leads to an increase in heart rate, a decrease in blood pressure, and a relaxation of the muscles. Redness of the eyes, dry mouth, overheating, or feeling cold are also among the symptoms seen.
After a while, slowing down in time, sensory perception disturbances (especially exaggerated perception) occur. Memory and learning are weakened, thinking and problem-solving speed slow down. The person relaxes physically and coordination is impaired. There is an extreme state of euphoria, characterized by tantrums. People can talk a lot compared to normal. After use, a rise in the appetite may be observed, especially towards sugary foods.
Sometimes, after these symptoms, intense negative emotions such as anxiety, fear, restlessness, or a state of depression may also occur. The severity of these feelings differs depending on the dosage used, the way of use, and the current mood of the person. Some people may experience permanent lethargy, emotional instability, impaired motor movements, and chest tightness that spreads to non-use times in the process.
The duration of the action of cannabis varies according to the amount and type of use. Its effect lasts for an average of 3 hours when it is used in the form of a cigarette. Contrary to popular belief, when the effect period expires, it is not removed from the body as quickly. Especially in the UK, young people trying to balance the psychosomatic effects of marijuana use with paranoia, social phobia, panic attack, and insecurity with the fake Zanax depression drug, which is easily accessible in the market recently, are unwittingly caught in a much more severe addiction, disconnected from social life and in their educational lives. They are starting to have big problems.
Treatment of cannabis addiction includes studies such as decontamination of the person from the substance, reducing the withdrawal symptoms experienced, preventing relapse, treatment of possible psychological disorders accompanying addiction, eliminating vital problems that may trigger use, and gaining a healthy coping skill with emotions. All these studies are planned individually within the framework of the person’s usage history and personal predispositions-needs.
Success in addiction treatment varies according to the person, environment, and method. The most important factor that increases the success in treatment is the willingness and determination of the person. While the addict is trying to change himself, his family must also agree to undergo changes. At this point, the support of the family is important.
Stopping use alone is not a sufficient treatment. Every addiction has gaps filled in a person’s life. As the disease becomes chronic, the areas filled with addiction expand, swallowing all the other resources the person feeds on, such as black holes. Taking a person in such a situation away from his dependence is like taking a piece of himself; The broken part must be filled with healthy equivalents.
Otherwise, after a while, the person may lose their recovery motivation and return to their old habit. Psychotherapy is one of the cornerstones of permanent healing in order to reach the inner resources that already exist in the person and to acquire new vital skills.
Drug Withdrawal Syndrome and Cannabis
Withdrawal syndrome is a clinical picture characterized by a variety of undesirable symptoms due to the sudden discontinuation of use or reduction of the dose while continuously using an addictive substance. This table can only be eliminated by repeating the addictive substance. With this aspect, withdrawal syndrome is a process that encourages the necessity of taking the substance continuously and it is the most important indicator that physical dependence on the substance used has developed.
With this feature, withdrawal syndrome defines both that the addictive substance is stopped suddenly by the user, and that the substance user is in search of a substance in a compulsive manner. The compulsive desire to find and use substances here is aimed at avoiding the withdrawal crisis and not experiencing this crisis.
While different substances may produce different withdrawal symptoms, some different substances may also produce similar withdrawal symptoms. In this case, symptoms due to the withdrawal of one substance can be completely relieved or alleviated by the other substance. This situation is called cross-dependency. Among the substances that are cross-dependent, there is often the development of cross-tolerance. Benzodiazepines and ethanol are two different types of addictive substances that can be given as examples for the development of cross-dependency and tolerance.
Withdrawal symptoms usually begin within a few hours of stopping the substance use. The onset time is directly proportional to the time of complete metabolism and removal of the substance from the body. When a drug or substance that is an antagonist of the addictive substance is administered, withdrawal symptoms appear much more rapidly and more severely.
For example, administering the antagonist naloxone to morphine addicts causes the symptoms of morphine withdrawal to appear very quickly and very severely. Using this feature, a morphine-dependent experimental animal model was created. The naloxone-induced withdrawal syndrome model is frequently used in experimental research. The severity of the withdrawal crisis can be fatal, depending on the duration of use and the degree of physical dependence that develops.
During a deprivation crisis, all of these symptoms may not be seen. Depending on the nature of the substance used and the degree of addiction, one or more of these may occur in different severities. Sometimes only one symptom can be fatal. These symptoms are very painful, and the person who initially tried the substance for pleasure must continue using the substance after the withdrawal crisis occurs to avoid this crisis. Withdrawal crisis is the most influential factor in maintaining substance addiction, along with the development of tolerance.
It is believed that tolerance and addiction have a close relationship. Withdrawal syndrome is thought to be a reflection of the body’s adjustments to the substance used by activating various compensatory mechanisms. Accordingly, withdrawal symptoms occur as a result of the introduction of homeostatic mechanisms to compensate for the physiological changes caused by the substance used continuously.
When the drug or substance use is discontinued and its effects are eliminated, the period of reorganization of this new state of the body is expressed as withdrawal syndrome and the physiological changes seen in the withdrawal period usually occur in a severe and opposite direction to the effects of the drug. For example, constipation is one of the most prominent effects seen during heroin use, and one of the important symptoms of heroin withdrawal syndrome is the opposite symptom, diarrhea. Although there are many data indicating a close relationship between tolerance and addiction, this relationship is not always valid and individual differences are in question.
The severity of withdrawal syndrome also varies between substances. While the withdrawal syndrome, which occurs with some substances, is very mild, it can be severe with some, which can lead to death. The severity of the withdrawal syndrome is also related to the dose and duration of use of the substance. Another important factor that determines the severity is the body’s capacity to metabolize the substance. If the body metabolizes the substance too slowly, the duration and severity of the withdrawal syndrome decrease in direct proportion to the slowness of metabolism.
Cannabis Withdrawal in Particular
In some people who use cannabis with tetrahydrocannabinol (THC), the absence or very mild withdrawal syndrome is associated with the slowness of THC metabolism. Some important changes occur in the neurotransmitter systems during the exposure and withdrawal period. Some neurochemicals increase and some decrease, and these changes may differ in both periods, and they are also related to the emotions felt during substance intake and withdrawal.
Withdrawal syndrome is a painful and undesirable condition for the addict. The desire not to enter withdrawal syndrome also contributes to the continuation of substance use. The central nervous system changes that cause physical dependence and therefore withdrawal syndrome cannot be fully explained. Although some theories have been put forward on this subject, they are mostly aimed at explaining morphine addiction and have not yet been definitively proven.
According to one view, when exposed to a substance chronically, a certain nerve pathway in the central system is inhibited. In this case, some backup paths that were inactive before the substance is used become active. When the substance use is stopped suddenly, the normal path becomes active again, but as the backup roads are active at this time, withdrawal syndrome symptoms occur.
According to another theory, the supersensitivity (increased sensitivity) that emerges over time in postsynaptic receptors is responsible for the formation of physical dependence and withdrawal syndrome. Accordingly, the addictive substance inhibits neuro mediator release at a certain nerve end. The decrease of the neuro mediator in the synapse causes an increase in the number of receptors in the postsynaptic membrane. If the substance is cut suddenly after this adaptation develops, the neuro mediator starts to be released as before, but it creates more severe effects in proportion to the increasing number of receptors at the postsynaptic level.
According to another theory put forward to explain morphine-type addiction, it is assumed that an opioidergic pathway continues its functions by inhibiting another pathway. When morphine is used for a long time, the said inhibitory pathway is kept active by the activation of postsynaptic receptors. When morphine is stopped suddenly, the inhibitory effect of the drug disappears in the postsynaptic region and thus the excitatory symptoms of withdrawal syndrome emerge. According to one theory, if the addictive substance is used for a long time, it has been suggested that the efficiency of the signal transduction system, which is interlocked with the receptors of this substance in the central nervous system, increases latently.
Accordingly, the continuous activation of the relevant receptor in the neuron membrane during chronic use of a substance such as morphine activates or inhibits effector macromolecules that are coupled with the receptor and transduces the signal from it, and causes contra-adaptive type changes in effector activity without any change in the receptor. These changes, which remain silent during the drug intake, become dominant from the moment the drug is discontinued and cause the emergence of withdrawal syndrome.
Cannabis Withdrawal: Rewarding and Addicting Characteristics of Cannabinoids
Although it is well known that cannabis and its derivatives are addictive, the development of physical dependence and withdrawal syndrome in cannabis addicts is a controversial issue. According to some researchers, only psychological dependence on cannabis develops, physical dependence and withdrawal syndrome either do not develop at all or progress with very mild symptoms compared to, for example, opiates. This view has significantly lost its scientific validity today.
The most important factors maintaining addiction in cannabis addicts include experiencing or fear of withdrawal symptoms, and withdrawal syndrome has been described in marijuana smokers. Although withdrawal symptoms that occur in humans after quitting cannabis cause problems in some addicts, according to DSM-IV, cannabis withdrawal symptoms are not very significant clinically. However, DSM-V has identified and considered cannabis withdrawal symptoms.
The most important reason for relatively mild cannabis withdrawal is the longer elimination half-life of delta-9-THC compared to substances such as alcohol, cocaine, and opioids. Recent research has shown that clinical evidence that cannabis causes withdrawal syndrome and physical dependence is so real that it is beyond dispute.
The use of the cannabis plant to change consciousness, to get drunk, to get pleasure, or to get high goes back to 5000 years ago. The main psychoactive substance of this plant is delta-9-THC and it is known that its addictive effect is directly related to its rewarding effect. Therefore, it is seen that delta-9-‘TCA is generally used in studies related to addiction in animals.
Tolerance develops rapidly in experimental animals to the effects of THC on operant behaviors. Depending on the dose and route of administration, a kind of tolerance may develop within 5-6 days to repeated doses of THC. This tolerance may persist for more than a month after the substance is completely withdrawn. There is also cross-tolerance between THC and its 11-hydroxy metabolite. In addition, while tolerance develops within a few days to the effect of THC increasing motor activity, there is no tolerance to its anorexic and self-distinguishing effects.
There is no relationship between changes in absorption, metabolism, or distribution of the substance and the development of tolerance. There is some controversy regarding the development of tolerance to cannabinoids and their derivatives in humans. Many marijuana users report an increase in effects that can be regarded as sensitization or reverse tolerance rather than a decrease in some of the effects during the period of continuous use of the substance. However, sensitization could not be demonstrated precisely in laboratory studies, neither in experimental animals nor in humans.
Sensitization or reverse tolerance was observed only outside of the laboratory. There may be various reasons for this. The most important of these is the dose and frequency of use. In laboratory studies, the dose which is given and the frequency of taking this dose are predetermined and the user has to adjust, for example, the total number of marijuana cigarettes to be taken and the frequency of taking it. In practice, users learn to inhale more effectively, meaning they are free to use more than a certain amount of marijuana.
Therefore, their use of the substance is purely for more enjoyment, and each individual user will use the substance at the frequency and dose that he or she can enjoy the most. Consequently to some of the effects of cannabinoids, just as with other addictive substances. We can say that tolerance develops and the nature and severity of the tolerance that develops depends on the person, the dose, and the frequency of use.
Cannabinoid Addiction and Withdrawal Syndrome
Because it is difficult to create a valid and reliable model for testing the rewarding and pleasurable effects of cannabinoids in humans, the “drug discrimination” method, which is a model that most accurately evaluates the interoceptive stimulating effect of drugs in animals, is used in cannabinoid research. It is one of the most important tests used. This method is a behavioral model that enables the intra-sensory effects of drugs to be used as discriminative stimuli in the operant conditioning mechanism and to compare the internal sensory effects created by different drugs.
Delta-9-THC is the most commonly used training drug in cannabinoid discrimination studies. It is understood that the discriminative stimulant effect created by Delta-9-THC is selectively specific to substances that bind only to the CB1 receptor. That is, only other cannabinoids replace delta-9-THC in animals trained to differentiate delta-9-THC from saline. In addition, there is a clear relationship between delta-9-THC’s substitution effects and their binding affinities to CB1 receptors. A similar relationship has been observed between the substitution of delta-9-THC by other natural psychoactive cannabinoids and their subjective pleasurable effects in humans.
Cannabinoids, and particularly potent synthetic cannabinoids, have also been used as training drugs in drug differentiation. For example, in an experiment where CP55,940 was used as a training drug, delta-9-THC and WIN55,212-2 were not only replaced by the training drug but also significant differences were observed between the effect they exhibited and the displacing rates of CP55,940 in receptor binding. a relationship has been identified.
In another study where WIN55,212-2 was used as an educational drug, CP55,940 and delta-9-THC led to a complete generalization, while this distinctive effect created by delta-9-THC and other synthetic cannabinoids was the antagonist SR-141716A. it was fully rejected by its pre-application. These observations reveal that the distinctive effects of cannabinoids are related to CB1 receptor activation. What is meant by generalization here is that all drugs used in the test setup produce similar effects or replace each other.
Unlike the other CB1 agonists we have listed above, different results were obtained in the discrimination tests in studies where anandamide, an endogenous cannabinoid, was used as a test drug. When anandamide was tested in studies in which experimental animals were trained to distinguish delta-9-THC from saline, the generalization either did not materialize at all (i.e., anandamide had no effect similar to or substituted for delta-9-THC) or was high enough to be considered toxic, inhibiting anandamide behavior. doses.
In these studies, the role that anandamide may play in rapid metabolism in these observations has not been overlooked. In studies using R-methanadamide, one of the more stable analogues of anandamide, a complete generalization was observed in the direction of expectations. In other words, R-methanandamide showed a similar discrimination profile with other agonist drugs.
The synergistic relationship observed between cannabinoids and the rewarding effects of opioids are also observed among the withdrawal symptoms of these substances. For example, injection of naloxone in rats with developed physical dependence on cannabinoids results in a withdrawal syndrome similar to opioids. Similarly, administration of the CB1 receptor antagonist SR-141716A in opioid-dependent rats also causes an opioid withdrawal syndrome.
The severity of withdrawal symptoms occurring in opioid-dependent animals is significantly attenuated by cannabinoids. Cross tolerance develops between morphine and delta-9-THC, and there is no change in the amount of cannabinoid receptor binding in the brains of animals that have developed tolerance to morphine. In addition, the fact that there is no change in the amount of binding to opiate receptors in the brain of animals with tolerance to delta-9-THC indicates that the interaction observed between these two systems occurs during post-receptor events in which second messengers and various kinases are involved.
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