The following excerpt describes the clinical presentation of cannabis withdrawal and its treatment.
The existence of a degree of dependence on cannabis is demonstrated by the fact that discontinuation after prolonged use is usually accompanied by a withdrawal syndrome. This phenomenon has been documented both in experimental animals and in humans and is characterized by the release of CRH1 and a specific neurobiological response within the amygdala. This response includes, in addition to induction of AEA hydrolysis, upregulation of the transcription factor c-Fos2. The C3435T polymorphism of the ABCB1 gene affects the distribution of THC in tissues, producing increased concentrations of THC in certain tissues and thereby favoring both its psychotropic effects and the propensity toward dependence (Benyamina et al., 2009). Cannabis withdrawal syndrome generally does not concern patients who use cannabis for therapeutic purposes, since THC is not necessary in all cases, and discontinuation of THC does not inevitably lead to withdrawal. Among cases in which THC is necessary, those using very small quantities (e.g., autism spectrum disorders, certain epileptic syndromes) likewise do not usually develop dependence. In autism, for example, a mixture with a CBD:THC ratio of approximately 20:1 is commonly used. In other conditions, such as multiple sclerosis, neoplastic disease, or dementia syndromes accompanied by agitation and anxiety in the very elderly, dependence on cannabis is usually the least significant problem faced by the patient. Many of these individuals are already dependent on opioids, neuroleptics, or antiepileptic drugs; their social integration and functional capacity are often adversely affected for multiple reasons, and the life expectancy of many of these patients is limited. From a diagnostic standpoint, the symptoms of cannabis withdrawal syndrome are classified as major and supportive. They may include the following:
Irritability, anger, aggressiveness
Restlessness
Anxiety
Sleep disturbances (insomnia or disturbing dreams)
Decreased appetite
Weight loss
Mood changes (depression)
Difficulty concentrating
Headache
Sweating
Fever, chills
Nausea
Gastrointestinal discomfort (e.g., abdominal pain)
Nonspecific tremulous syndromes
For diagnosis, at least three major symptoms and at least one supportive symptom are required (Connor et al., 2022). Craving for cannabis and the associated persistent ideation constitute a stable feature but are not in themselves diagnostic, although they may render the individual functionally impaired. Some of these symptoms may provoke anger, the expression of which may range from mild irritability and dysphoria to violent rage. Within the context of cannabis withdrawal syndrome, affected individuals may exhibit intimidating, threatening, or even violent behavior [Smith et al., (2013), Maniglio, (2015)]. The severity and duration of these symptoms may vary considerably. Onset typically occurs 24-48 hours after cessation, while peak intensity of most symptoms is observed between the second and sixth day. In heavy cannabis users some symptoms may persist for up to three weeks or longer. The appearance and duration of withdrawal symptoms may also depend on factors such as frequency and duration of use as well as individual metabolic differences. In any case, although there is no intrinsic threat to life or general health, guidance from the treating physician, or, in the case of non-medical users, from a specialist in addiction medicine, is advisable. In particular, when anger is prominent, protective measures should be taken for both the patient and the surrounding environment until the condition stabilizes. Physicians may occasionally observe minor withdrawal manifestations during phases of THC dose adjustment, especially when the dose is reduced. Similar manifestations may occur when intermittent therapeutic regimens are applied in an attempt to reverse tolerance, when CBD doses are reduced while THC doses remain unchanged, or when substantial dose reductions are required prior to general anesthesia, forensic examination, occupational drug testing, or similar circumstances. In the vast majority of such cases withdrawal phenomena are limited to irritability and difficulty initiating sleep, usually lasting 1-3 days. This occurs because even abrupt discontinuation of THC does not usually leave the organism entirely without cannabinoid activity: cannabinoids stored in "slow", lipid-rich tissues are mobilized, allowing a somewhat smoother transition, less smooth, however, in very lean individuals. The organism of a chronic user can experience absolute THC deprivation only if a CB1R antagonist is administered, something that is currently impracticable in humans3. Management of cannabis withdrawal syndrome usually requires only supportive care and symptomatic treatment. In non-medical users wishing to discontinue cannabis, preparatory counseling is advisable, focusing on anticipation of possible symptoms and clarification of expectations associated with cannabis use. This is followed by supportive care, primarily psychological support or philosophical counseling. Such measures improve adherence and reduce anxiety. In some cases behavioral or cognitive therapy may be required in order to address relapse tendencies. Frequently a strong need arises for family or social support and assistance, particularly when the problems originate within, or extend into the family environment (Connor et al., 2022).
Irritability and anxiety: Managed with relaxation techniques and exercises and, where appropriate, with counseling or supportive psychotherapy.
Insomnia: Managed through the implementation of sleep hygiene practices, relaxation techniques, and/or short-term use of sleep aids if considered necessary by the treating physician. Melatonin represents a suitable initial option, since it does not carry a risk of dependence.
Headache or other painful symptoms: Managed with analgesics of varying potency, used short-term, with caution, and according to the clinical context.
Nausea and gastrointestinal discomfort: Managed with dietary adjustments, adequate hydration, and, where appropriate, pharmacological treatment.