Vyvanse and Cannabis Interaction Profile: What Patients and Prescribers Need to Know

Does Cannabis Appear in the Vyvanse Label?

The Vyvanse drug interaction table covers MAO inhibitors, which are contraindicated during use and within 14 days of stopping; serotonergic drugs such as SSRIs, SNRIs and triptans; CYP2D6 inhibitors; urinary alkalinizing agents such as sodium bicarbonate; urinary acidifying agents such as ascorbic acid; and tricyclic antidepressants [1]. Cannabis and THC are not on that list [1].

Lisdexamfetamine is an inactive prodrug converted to dextroamphetamine and l-lysine mainly in the blood by red blood cells, not by cytochrome P450 enzymes, and the intact prodrug does not bind norepinephrine or dopamine reuptake sites in vitro [1]. Amphetamine blocks reuptake of norepinephrine and dopamine into the presynaptic neuron and increases release of both [1]. Whether cannabis changes Vyvanse exposure or effects has not been established.

Cardiovascular Effects: What Is Documented

The label states that CNS stimulants raise blood pressure by a mean of about 2 to 4 mm Hg and heart rate by about 3 to 6 bpm, that some patients have larger increases, and that all patients on Vyvanse should be monitored for tachycardia and hypertension [1]. It says to avoid Vyvanse in people with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease or other serious cardiac disease, and notes that sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease treated with CNS stimulants at the recommended ADHD dosage [1].

In the 4-week adult ADHD trial, increased blood pressure was reported in 3% of Vyvanse patients versus 0% on placebo, increased heart rate in 2% versus 0%, and palpitations in 2% versus 0% [1]. These figures come from trials of Vyvanse alone; the effect of adding cannabis on heart rate or blood pressure is unknown.

Psychiatric Effects and the Label's Screening List

The label warns that stimulants may worsen behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder, and may induce a manic or mixed episode in bipolar disorder [1]. Before starting treatment it says to screen for risk factors for a manic episode, giving as examples comorbid or prior depressive symptoms and a family history of suicide, bipolar disorder or depression [1]. Cannabis is not among those examples [1].

In pooled short-term, placebo-controlled trials of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of stimulant-treated patients compared with 0% on placebo, and the label says to consider discontinuing Vyvanse if such symptoms occur [1].

Does Cannabis Help ADHD Symptoms?

The one study cited here on this question is a qualitative analysis of online ADHD forums, not a clinical trial. It identified 268 threads, randomly selected 20% of them (55 threads) and coded 401 posts [3]. Of those posts, 25% described cannabis as therapeutic for ADHD, 8% as harmful, 5% as both and 2% as having no effect [3]. The authors noted that there are no clinical recommendations or systematic research supporting the beneficial effects of cannabis for ADHD [3].

What a 2022 Guideline Says About Stimulants and Substance Use

A 2022 clinical practice guideline, built with the GRADE approach, addressed the treatment of ADHD in people with substance use disorder, including cannabis use disorder [2]. In people with ADHD and cannabis use disorder it recommends atomoxetine to improve ADHD symptoms (weak recommendation) and does not recommend it to reduce cannabis use (weak recommendation) [2]. For ADHD with any substance use disorder it recommends psychostimulants, the class that includes lisdexamfetamine, to improve ADHD symptoms (weak recommendation) and not to reduce substance use (weak recommendation) [2]. Its authors concluded that atomoxetine and psychostimulants appear safe in patients with any substance use disorder (strong recommendation) [2]. That is a statement about treating ADHD in people with substance use disorders, not a finding about taking cannabis and a stimulant at the same time.

Real-World Data in Cannabis Use Disorder

One observational dataset touches both drugs. A Swedish register study followed 51,947 people aged 16 to 64 with a first diagnosis of cannabis use disorder between 2006 and 2021, and compared hospitalisation risk during periods on and off each psychiatric medication within the same person [4]. Lisdexamfetamine use was associated with a lower risk of hospitalisation for substance use disorder (adjusted hazard ratio 0.74, 95% CI 0.69 to 0.79) [4]. The authors described the analysis as exploratory and said the pattern across ADHD, opioid or alcohol use disorder, and treatment-resistant schizophrenia medications likely reflects underlying clinical trajectories rather than direct therapeutic effects on cannabis use disorder [4].

Sleep and Appetite: The Label's Adult ADHD Numbers

In the 4-week adult ADHD trial, the label reported insomnia in 27% of Vyvanse patients versus 8% on placebo, decreased appetite in 27% versus 2%, and dry mouth in 26% versus 3% [1]. The label says to take Vyvanse in the morning and avoid afternoon doses because of insomnia [1].

What the Label Asks Prescribers to Watch

Before treatment, the label asks for a cardiac assessment including history, family history of sudden death or ventricular arrhythmia, and physical exam, and an evaluation for tics or Tourette's syndrome [1]. During treatment it asks for blood pressure and pulse monitoring and watching for new psychiatric symptoms [1]. Vyvanse also carries a boxed warning for abuse, misuse and addiction: the label describes a high potential for abuse, asks prescribers to assess each patient's risk before prescribing, and to reassess and monitor frequently throughout treatment [1]. Lisdexamfetamine is a prodrug of amphetamine and a Schedule II controlled substance [1].