The results of this study indicate that cannabis withdrawal symptoms are highly prevalent among frequent cannabis users in the U.S. general population. The most common withdrawal symptoms were feeling weak/tired, hypersomnia, sleeping, yawning, depression and feeling nervous or anxious, similar to symptoms found in volunteers in inpatient laboratory studies 13, 14, 26
and in patients.20, 19
Further, cannabis withdrawal, consistently identified by 11 symptoms, differentiated into two factors, one characterized by weakness and the other characterized by anxiety and depression. The findings are based on the largest and most representative sample of frequent cannabis users studied to date.
The largest early clinical study of cannabis effects, a study of 53 men hospitalized for 21–42 days, indicated that in the week following cessation of cannabis use, symptoms commonly reported included sleep disturbance (89%), restlessness (89%), and irritability (62%).9
In more recent prospective outpatient and inpatient studies, 13–18
no cannabis withdrawal symptom emerged in all studies. However, symptoms commonly reported were anxiety (after low dose13
) 14, 16, 18
and symptoms of physical discomfort. 16–18
Irritability was also commonly found, 13–18
although in one study 13
only in the low consumption condition; in a second study 14
only in the high consumption condition; and in a third study, evidence was only “moderate.”17
The anxiety/depression withdrawal symptoms found in these studies corresponded well to our second factor, providing important consistency between this large general population sample and previous prospective outpatient and inpatient studies. Weakness withdrawal symptoms were also found in lab studies 13, 14
and in a clinical study of adolescents, especially males. 20
While fatigue was not found during cannabis withdrawal among cannabis users in their home environments, 17
the other studies in conjunction with the present findings indicate that these symptoms merit further investigation. Irritability and anxiety may receive greater clinical consensus as regular features of cannabis withdrawal because they are subjectively and clinically striking compared to fatigue and related symptoms. Varying emergence of weakness and depression/anxiety symptoms as part of cannabis withdrawal may also relate to varying levels of Δ9
-THC in cannabis and varying levels of other cannabinoids that, while weaker than Δ9
-THC, may interact with Δ9
-THC to alter its effects. 42
Our results also indicated support for the validity of the cannabis withdrawal syndrome in the general population, as clinical distress/impairment and using to relieve or avoid symptoms were strongly related to both depression/anxiety and weakness in both samples. We did not find that age of onset of cannabis use predicted cannabis weakness or depression/anxiety withdrawal symptoms in either sample. This could be due to restricted variance of this variable, as early age of onset is highly associated with frequent cannabis use. 43, 44
We also found that shorter duration of cannabis use predicted more withdrawal symptoms. This could be because shorter-term users did not have tolerance to cannabis, as might be expected of longer-term or dependent users. These validators should be further addressed in future laboratory studies to establish more specific mechanisms. Finally, weakness/fatigue cannabis withdrawal symptoms in our study were associated with a family history of drug problems in the subset of frequent cannabis only users, while the depression/anxiety withdrawal symptoms were not. Further evidence of the familial nature of these two types of symptoms would contribute important information towards understanding their etiology.
Budney and colleagues showed that psychopathology measured on symptom scales was related to cannabis withdrawal 19
in patients seeking treatment for marijuana problems, but no previous studies addressed the relationship of cannabis withdrawal to DSM-IV disorders. We studied primary major depression, generalized anxiety and panic disorder because their symptoms partially overlap with cannabis withdrawal symptoms. We studied personality disorders because this has not been done before and the high prevalence of personality disorders in “healthy” volunteers for research studies 27
may have influenced earlier findings. The association of primary panic disorder or major depression with cannabis depression/anxiety withdrawal symptoms suggests possible common vulnerability, meriting further investigation. The association of personality disorders with depression/anxiety but not weakness withdrawal symptoms in the subsample suggests further study of weakness symptoms in participants screened for personality as well as Axis I psychopathology, as weakness withdrawal symptoms may emerge more among individuals without personality disorders, and prior laboratory and prospective studies screened for Axis I psychopathology only.
Study limitations are noted. First, withdrawal symptoms were measured via retrospective structured self-report rather than observation. However, the coherence of our findings on the anxiety withdrawal symptoms with earlier studies adds strength to the aggregated literature on this aspect of cannabis withdrawal, while the finding on the weakness factor merits further investigation. Second, the symptoms analyzed included those listed for other substances in DSM-IV. While multiple symptoms of anxiety, physical discomfort, and negative affect were included, irritability was not. As noted above, a number of studies show irritability as a cannabis withdrawal symptom. While our factors might have been altered if we had included irritability, irritability tends to co-occur with anxiety, depression, and insomnia1, 7, 22
suggesting that the addition of irritability would not result in a major restructuring of the factors. However, future epidemiologic studies on cannabis withdrawal should clearly include irritability. Third, we did not have precise measures of the amount of Δ9
-THC ingested and cannabis potency and efficiency of smoked self-administration can vary considerably. Most of those in our sample appear to have been heavily exposed to cannabis during their period of heaviest use, but we cannot precisely quantify the relationship of cannabis ingested with the emergence of withdrawal symptoms on abstinence. Fourth, information is lacking on whether those in the sample who used cannabis 3–4 times a week used cannabis on consecutive days. However, these respondents constituted a minority of the sample, and results of the factor analysis were virtually identical when the 3–4x/week users were removed from the sample. Fifth, it is possible that individual symptoms we identified might be related to other conditions, e.g., that the individual symptom of weakness might reflect postural hypertension, a direct effect of cannabis use. 45
However, our wording of the question on the timing of the symptoms relative to cannabis use (“the morning after, or in the first few days after”) in addition to the empirical clustering of symptoms found reduces the possibility that the full syndrome reported is a conglomeration of individual symptoms resulting from other diverse conditions.
Advantages of the study are also noted. The similarities between the full group and the subset suggested that withdrawal symptoms of cannabis were not being confused with other substances in the full group. First, the large and representative sample afforded a new vantage point on cannabis withdrawal. Further, the subset of respondents who did not abuse other substances provided an important opportunity to confirm that cannabis withdrawal symptoms reported by the larger group were not due to other substances they had used. Second, weighted factor analysis of the symptoms provided an organized quantitative method of arriving at a set of items that measured two aspects of cannabis withdrawal well. While replication of the factor structure is clearly needed, this study is the first to provide information from such analyses. Third, the measures included in the study enabled us to address important historical and psychiatric correlates of the two factors, contributing new and valuable information on clinical significance and associated aspects of psychiatric history.
In demonstrating a syndrome, some variability in its presentation does not negate its existence. For example, few would now argue against the existence of an alcohol withdrawal syndrome, despite well-recognized variability in its clinical features. 46
While such variability in the presentation of cannabis withdrawal may relate to the amount of the active substance ingested, it is also likely to be related to individual variation in the pharmacokinetics and pharmacodynamics of the psychoactive elements in cannabis. A better understanding of these processes appears important in understanding the development of cannabis disorders and their treatment. Additionally, we found gender and age effects on the number of depression/anxiety and weakness symptoms reported. Demographic differences in the presentation of withdrawal symptoms are not unique to cannabis, 47
but should be further investigated in future studies.
The findings of this study have several implications. First, the prevalence of cannabis withdrawal symptoms among frequent cannabis users in the U.S. general population indicates a problem national in scope that is not limited to patients or individuals who willing to volunteer for inpatient laboratory studies. Given the projected increase in cannabis use in the coming decade, 4
the established increase in potency of the cannabis in general distribution in the U.S., 2
and evidence that higher potency increases the reward properties of cannabis, 27
the prevalence of cannabis withdrawal among users highlights the importance of understanding such withdrawal better. Second, the findings suggest that clinicians should be aware of the potential for cannabis withdrawal symptoms in frequent cannabis users, even if the primary drug is a different substance. Due to the common use of marijuana among patients in substance abuse treatment, the occurrence of cannabis withdrawal may need closer attention than previously believed. Post-hospital marijuana use predicts poor outcome of dependence on other substances, 48
and cannabis withdrawal symptoms may contribute to such poor outcome. Coverage of cannabis withdrawal symptoms in research evaluations can provide more information on this point, potentially assisting in identification of patients at risk for poor outcome due to these symptoms. Third, the study findings further support addition of cannabis withdrawal to DSM-V and ICD-11. Our analyses did not directly investigate a valid threshold, but a 3-symptom threshold would be consistent with other withdrawal categories in DSM-IV and would identify about one-third of all frequent cannabis users. Lastly, the findings suggest that an understanding of the etiology of these symptoms would be worthwhile. Such an understanding should contribute to the development of better treatments for patients with cannabis use disorders, an increasing public health problem.