In this prospective cohort study of older adults treated with medical cannabis, we have shown that cannabis treatment for six months was associated with improvements in IADL and GDS, as well as a reduction in pain and opioid use. No significant changes were found in ADL or in appetite following cannabis treatment.

The effect of cannabis on scales of functional status in older adults was not assessed in previous studies. A study of younger patients, in which only 5% of the population was above 70 years of age, showed that cannabis improved areas of bodily pain, physical functioning, and social functioning, but limitations due to either physical or emotional problems were not changed [24]. Another study of older adults in Colorado and Illinois showed an association between more frequent cannabis use and higher scores on health-related quality of life and healthcare utilization scales [25]. The Lawton IADL include using a telephone, shopping, preparing food, housekeeping, laundry, finance managing, and responsibility for medications [16]. ADL include bathing, dressing, continence, feeding, and toileting [15]. Among older adults, there is a significant difference between age groups, with younger patients having a higher probability of achieving improvement in IADL scores. In spite of this, among those that improved their IADL scores, the median age was 78, i.e., almost half of the patients were over 80 years old. When evaluating the association of age and improvement in ADL or IADL scores in multivariable analysis, there was no significant association to age under 80. On the contrary, there was a significant association in multivariable analysis between male sex and improvement in IADL scores. Emerging research has illuminated intriguing sex-specific patterns in functional decline. While there is a general consensus that women tend to outlive men, studies suggest that this longevity may not necessarily translate to greater functional independence. Some investigations indicate that women may experience a steeper decline in IADL capabilities compared to men, potentially attributed to factors such as hormonal changes and a higher prevalence of certain chronic conditions [26].

Neither the number of times cannabis was used daily nor the THC content of the cannabis were associated with changes in ADL or IADL scores in the multivariable analysis. The minimally important changes for both Katz ADL and Lawton IADL were determined to be around half a point [27]. In our cohort, the mean changes in ADL and IADL scores were 0.1 and 0.6, respectively, before and after cannabis treatment. Therefore, the change in IADL score was clinically significant and probably correlates with the overall satisfaction obtained from the treatment. The mechanism by which cannabis possibly improves the functional status is by improving chronic pain, mood, and general well-being. Another potential mechanism is the reductions in certain drugs, such as benzodiazepines, which have been shown to impact functional status in older adults [28,29]. All these changes enable older adults to function more independently in society, but these changes cannot improve functions such as continence, toileting, or dressing, which are reflected in the ADL scores. Thus, it is not surprising that medical cannabis improves IADL but not ADL.

The main indication for cannabis use in our study was neuropathic pain. This is the most common indication for cannabis in Israel as well as in other countries [11,30,31]. It should be noted that the proportion of patients with malignancies was smaller than expected, but this is due to lack of oncologists in the clinic where the study was conducted. The number of patients with an indication of Parkinson’s disease was also relatively high, as this is indication is found in less than 1% of patients in the general population [31]. This difference is probably attributed to the older age of the population in our study.

The most common route of administration for cannabis in our study was tinctures (cannabis oil). This route of administration is the most preferred for older adults and differs from younger individuals, especially those without a previous experience in smoking tobacco [32]. Consuming cannabis via this route prolongs the effect of cannabis, which is usually suitable for aiding chronic conditions.

The composition of cannabis products was heterogenous among our study group. Most of the patients used either CBD-rich cannabis or cannabis with equal amounts of THC and CBD. This finding is in line with other studies exploring the use of cannabis in older adults [11], and can be attributed to the will of both the prescribing physician and the patients to avoid adverse effects caused by high doses of THC. These adverse effects include gait and balance problems, primarily caused by the effects of THC [12]. Additionally, it is plausible that the anti-inflammatory properties of CBD contribute to the improvement in daily activities [33].

Two distinct patterns can be seen in our results: on the one hand, one-quarter of the patients decided to discontinue the treatment with cannabis after six months; on the other hand, almost all other patients reported that cannabis led to improvement in their overall condition, and two-thirds reported either moderate or significant improvement. These high rates of satisfaction can be explained by the high expectations from cannabis and its perceived efficacy in the general population [11,34]. The relatively large proportion of patients that stopped using cannabis supports the notion that cannabis is not a magical cure that can aid all illnesses.

The effectiveness of cannabis in addressing mood-related disorders and overall quality of life among older individuals has been substantiated through multiple investigations, including our own [10,11,35]. Our present outcomes concur with these findings, illustrating that cannabis contributes to the amelioration of depressive symptoms, as indicated by the GDS score, while also achieving discernible pain alleviation. The average alteration in GDS scores, measured as a change of 1.4 points, surpasses the established threshold of clinical significance, previously determined as 1.2 points [36]. When evaluating the association of age and improvement in GDS scores in multivariable analysis, there was a significant association with age under 80 compared to age above 80 years. However, neither the number of uses of cannabis every day nor the THC content of the cannabis were associated with changes in the GDS score in multivariable analysis.

The reduction in the VAS pain score after cannabis treatment is significant, both statistically and clinically. Clinically significant pain alleviation is characterized by a reduction of 2 points on a 0-to-10 numerical pain rating scale or a noteworthy reduction of 30% in pain intensity [37,38]. We demonstrate a reduction of 3.3 points of the average before and after the treatment. This significant reduction also explains the generally perceived effectiveness of cannabis and the reduction in other medications as the main indication for treatment in our cohort was pain reduction. Despite these remarkable numbers, which were reproduced in previous studies from our group [10], as well as other studies [11], the effectiveness of cannabis in treating chronic pain is still an issue of debate. Recent meta-analyses of randomized controlled trials and observational studies continue to conclude there is only weak evidence for the efficacy of cannabis for the treatment of chronic pain [39,40]. This discrepancy has also been discussed in the literature [41], and is attributed to the difficulty of reproducing cannabis studies between different countries and to the different constituents of cannabis, which are not identical in all studies.

Our findings also demonstrate the relatively favorable safety profile of cannabis therapy, as evidenced by the notably low incidence of adverse events necessitating medical intervention. In addition, less than 10% of the cohort defined the adverse effects as most severe. These observations align with the outcomes of our previous investigations involving older adult cohorts [10,35], as well as analogous comprehensive studies [11]. Dizziness, the most common adverse event in our study, is a well-known adverse event effect of cannabis. The profile of adverse effects was similar in our cohort of older adults compared to cohorts of younger adults treated with cannabis [42].

As evidenced in our prior investigation [10], a noteworthy outcome emerged with the implementation of cannabis treatment, namely a discernible reduction in the utilization of chronic medications. This transformation was particularly pronounced within the realm of analgesics, with opioids, in particular, exhibiting a marked decline in usage. The minimal clinically important difference for a reduction in opioid dosage was determined as a percentage change of 28.2% in the MME [43]. In our cohort, the reduction in opioid use met this criterion, as there was a reduction of 43.0% after cannabis treatment. In addition to this meaningful dose reduction, there was also a significant reduction in the pain VAS scores. Many studies have already assessed the opioid-sparing effect of cannabis, but it should be stated that this effect was also assessed in a recent meta-analysis, which found that the effects remain uncertain due to the very low certainty evidence [25]. We also saw a reduction in benzodiazepines and anti-hypertensives, but in a smaller fashion than with a previous cohort [10].

Cannabis has a known effect on appetite hormones [44,45]; nevertheless, the efficacy of cannabis treatment for improving appetite-related symptoms has not been consistently demonstrated in randomized controlled trials [20]. Our results are consistent with most of these studies, showing no net effect of cannabis on appetite: most patients reported no change and a similar number of patients reported an increase or decrease in appetite.

Our study has several limitations. First, the observational nature of our study can only allow us to determine association and not causality. Second, the study was conducted as a before–after study without a control group. Third, not all participants used the same kind, same dose, and same composition of cannabis. Fourth, most of the patients in the study were treated with cannabis for pain, limiting generalizability for other common indications, such as malignancy.