The purpose of this study is to see whether using ketamine to increase glutamate in the prefrontal cortex can reduce Multiple Sclerosis (MS) related fatigue. The investigator proposes a prospective, crossover, randomized, placebo-controlled study to assess the efficacy and safety of low, single dose Ketamine, to assess its efficacy and safety in patients with MS-related fatigue.

The study treatment is designed in two 28-day cycles: for each cycle, participants will receive study infusion on Day 1 and complete follow-up visits during Days 7 and 28. Participants are randomized 1:1 to receive either ketamine (active treatment) or saline solution (placebo treatment) for their first infusion. They will not be blinded to their study assignment: the study doctor will disclose their assigned treatment group.

After their first infusion cycle, participents will crossover to the other treatment group. Worded differently, if a participant received ketamine during their first infusion, they will receive placebo treatment during their second infusion. Conversely, if a participant received saline treatment during their first infusion, they will receive ketamine during their second infusion.

Inclusion Criteria:

1. Female and Male patients with any form of CDMS ages 18-65 inclusive
2. Report fatigue which is interfering with QOL
3. Able and willing to sign informed consent
4. Stable on DMT for at least 3 months prior to baseline visit
5. Not experiencing an MS relapse within 90 days prior to baseline visit.
6. Must agree to practice an acceptable method of contraception
7. Experiencing significant fatigue due to MS (MFIS of ≥10)

Exclusion Criteria:

1. Allergy to Ketamine

2. Taking medications which may interact with ketamine

3. Change in DMT within 3 months prior to baseline visit

4. MS relapse within 90 days of the baseline visit

5. Confirmed diagnosis of untreated Sleep Apnea

6. Confirmed diagnosis of periodic limb movement disorder

7. Serious infection in the 30 days prior to baseline visit.

8. Patients with significant comorbid conditions:

   1. Untreated hypertension (SBP>160, DBP>100 at baseline)
   2. Liver disease
   3. Significant renal disease
   4. History of cardiac arrhythmia
   5. Any comorbidities which at the opinion of the investigators post undue risk

9. Current alcohol or drug abuse

10. Participation in another interventional clinical trial in the past 3 months.

11. Pregnant or lactating

12. Any condition which in the opinion of the investigators will cause safety concerns for the patient, or inability to comply with the protocol.