The cannabis withdrawal phenomenon has received growing interest in recent years. Cannabis withdrawal does not typically cause significant medical or psychiatric problems as do opioid, alcohol, or benzodiazepine withdrawal [1], but implications of withdrawal symptoms include the risk of relapse and the well-being of patients [2].

A withdrawal syndrome is characterized by onset after cessation of drug use followed by a gradual return to baseline levels, and reversed by new drug use. Until recently, no official definition of a cannabis withdrawal was listed in the official diagnostic nomenclatures ICD-10 and DSM-IV.

With the recent publication of the DSM-5, a cannabis withdrawal syndrome is now officially recognized with defined criteria [3]. In the following, we shall review the evidence for these criteria as well as comment on criteria that are listed as ancillary in the DSM-5.

Status of the cannabis withdrawal syndrome

In 1994, Carroll and colleagues found that withdrawal was rarely endorsed by cannabis users, and Guttman scaling showed that only the most severely affected cannabis dependent patients reported cannabis withdrawal [4]. However, in the absence of specific criteria, respondents may not have interpreted symptoms that occurred after cannabis cessation as withdrawal symptoms. Later research has indeed produced a different picture [2].

Studies have found that the cannabis withdrawal syndrome appears to be comparable to the tobacco withdrawal syndrome [5, 6], and is associated with severity of cannabis problems at follow-up [7, 8]. Most symptoms of cannabis withdrawal increase immediately after cessation and decline over the next weeks [9–11], see however [12]. Additionally, studies have shown that the symptoms of cannabis withdrawal can be treated effectively with oral THC [13–15] and that sleep problems associated with cannabis withdrawal can be treated with zolpidem [16].

Specific symptoms of cannabis withdrawal listed in the proposal for DSM-5

Cannabis withdrawal has been recommended for inclusion in the DSM-5 with the following symptoms: A. Cessation of heavy and prolonged cannabis use; B. 3 or more of the following developments within several days after cessation: 1. Irritability; 2. Nervousness; 3. Sleep difficulty; 4. Decreased appetite; 5. Restlessness; 6. Depressed mood; 7. Physical symptoms and discomfort.

In the following, studies that have supported the inclusion of these symptoms are presented.

Irritability. Most studies give strong support to the relevance of irritability and anger as a common and significant symptom of cannabis withdrawal e.g. [7, 9, 11, 17–23]. Irritability and anger may have a later onset and a longer duration than most other withdrawal symptoms [11]. Additionally, more severe expressions of aggression, such as attacking someone physically, may occur later than milder symptoms of irritability [20].

Nervousness. Nervousness is also a commonly reported symptom [7, 8, 11, 17, 19–23]. Prospective research has found that nervousness associated with cannabis withdrawal is a source of significant distress [9], and that it gradually declines in severity after cannabis cessation [10, 11]. However, not all studies have supported the significance of nervousness as a symptom of cannabis withdrawal e.g. [18].

Sleep difficulty. Sleep difficulty or insomnia is also frequently reported as a withdrawal symptoms [7–9, 11, 17, 18, 20, 21], that decrease with time since cessation [10, 11, 18]. However, studies have found some uncertainty regarding the time course: prospective studies using self-report measures suggest that sleep problems decline fairly linearly after cessation of cannabis use [10, 11], whereas a study using polysomnogram data indicated that sleep quality declined gradually over 13 days with no reversal [24].

Decreased appetite or weight loss. Decreased appetite or weight loss has been robustly reported across studies [9, 11, 18–23] with a quick onset after cessation, followed by a relatively quick reversal [11].

Restlessness. Restlessness has generally been supported as a common and significant symptom of cannabis withdrawal [7–11, 17, 20, 21] with a slightly later onset than most symptoms [11].

Depressed mood. Depressed mood is also commonly reported, although not as often as nervousness or irritability [7, 8, 17, 19–21, 23]. Some prospective studies have failed to show that it follows a clear withdrawal pattern [11, 18], but other research supports its inclusion as a valid withdrawal symptom [9].

Physical symptoms. Physical symptoms such as stomach pain, shakiness/tremors, sweating, fever, chills or headache have been reported at variable rates, and generally at lower rates compared with other symptoms [7, 8], e.g. [17, 20–23], but some research has supported most of these symptoms as indications of withdrawal [9], see however [18].

Other symptoms

The withdrawal symptoms listed in the DSM-5 are not the only symptoms that have been studied in clinical and experimental research. Some of these other symptoms are likely to be highly correlated with symptoms in the DSM-5, and have been listed as symptoms that may also occur [3].

A frequently reported symptom is increased appetite which is about as common as decreased appetite [19–21], although Allsop and colleagues have reported that it is not valid as a withdrawal criterion [9].

One of the most commonly reported withdrawal symptoms not included in the DSM-5 is vivid unpleasant dreams, although it appears to be as common as the symptoms listed for the DSM-5 [8, 9, 11, 17, 18], see however [21]. The time course of these dreams differs from other symptoms studied with a later onset and a longer duration [11, 20]. Vivid, unpleasant dreams is not easily subsumed under any of the included symptoms in the DSM-5, but it is worth noting that strange and unpleasant dreams is listed in the DSM-5 criteria for amphetamine and cocaine withdrawal.

Methodological limitations in the existing literature

The literature described above shows a fairly consistent picture of the cannabis withdrawal symptoms that is largely in line with the proposal to include cannabis withdrawal in the DSM-5. However, the literature on cannabis withdrawal presents some methodological challenges. One potential limitation is the problem of demand characteristics. In psychology, demand characteristics refer to “the totality of cues which convey an experimental hypothesis to the subject” [25]. In this context, giving patients cues that a given instrument is designed to measure withdrawal from cannabis may prompt them to respond in ways that they perceive matches what they believe about withdrawal in general.

For instance, if patients believe that withdrawal is a temporary cluster of symptoms that begins after cessation of drug use, they may be more likely to report symptoms after cessation of use, and stop reporting these symptoms after a while. Such cues may range from having cannabis withdrawal in the heading of the questionnaire, over to asking on the same form how many days it has been since the subject last used cannabis, to having a cannabis craving scale on the same instrument. While previous literature has addressed some aspects of demand characteristics, e.g. by using filler items [9], using alternative headings, such as “Behavior Checklist” [18], or asking participants to fill in other measures simultaneously with marijuana craving questionnaires [11], all studies have been open about the study’s focus on marijuana cessation during the recruitment phase, and it has thus been clear to respondents that questions they have answered may specifically have been associated with marijuana. This includes the fact that participants have been asked to choose a quit date for marijuana, and that they have been asked if they used marijuana prior to entering the study.

No study has so far used the seven symptoms listed in the forthcoming DSM-5 together as the indicator of withdrawal. Studies have either used some of these symptoms or included other symptoms such as craving.

Finally, the cannabis withdrawal syndrome has not yet been studied in poly-substance using patients with the exception of one small cross-sectional study by Vorspan and colleagues that indicated that sleep disturbances, but not other cannabis withdrawal symptoms, were exacerbated in patients with co-morbid opioid dependence [26]. Arguably, there are good reasons for the omission of poly-substance using patient samples when establishing the validity and time course of the cannabis withdrawal syndrome. Other drugs may influence mood, physical discomfort, sleep, appetite and overall wellbeing which may well mask or exacerbate symptoms associated with cannabis withdrawal. However, poly-substance dependent patients make up a large proportion of patients in substance abuse treatment. If poly-substance abusing patients experience clinically significant cannabis withdrawal symptoms, psycho-education, behavioral and pharmacological interventions that target the cannabis withdrawal syndrome should be made available to such patients.

Aims of the present study

The present study was part of a larger study of residential treatment in Denmark, funded by the Ministry of Social Welfare.

The aim of this study was to assess the recommended withdrawal symptoms of cannabis in the DSM-5 through patient self-reports during detoxification in Danish residential rehabilitation centers measured over 4 weeks of early treatment.

The goals were:

1. To assess the time course of the DSM-5 cannabis withdrawal syndrome in relation to time elapsed since last use of cannabis. We hypothesized that the DSM-5 symptoms would follow a curvilinear time course from cessation of cannabis use characterized by an increase in severity immediately after cessation followed by a decrease. This was conducted by administering a scale consisting of all the criteria listed in the DSM-5 for cannabis withdrawal three times over four weeks of treatment. 2. To assess the time course of each individual symptom of withdrawal, including symptoms currently listed for other substances than cannabis, controlling for use of other drugs.

Patients with poly-substance abuse were ideal for this purpose. If only cannabis users were included in the study, this would potentially be a cue that the focus of the study was cannabis-related.